A Comprehensive Guide to the 2025 CPT Codes for Genetic Testing

Genetic testing plays a critical role in diagnosing hereditary conditions, guiding treatment decisions, and predicting disease risks. As technology advances, medical billing and coding must keep pace. The 2025 CPT code updates introduce several new genetic testing codes, impacting medical practices, laboratories, and insurance reimbursement.

If you handle medical coding, billing, or revenue cycle management, understanding these updates is crucial for accurate claims submission and compliance. This guide covers new 2025 CPT codes for genetic testing, billing guidelines, and reimbursement strategies.

Overview of 2025 CPT Code Changes for Genetic Testing

Current Procedural Terminology (CPT) codes are used in medical billing to report diagnostic procedures, including genetic tests. The genetic testing CPT codes are divided into three main categories:

• Tier 1 Molecular Pathology Codes – Standardized tests for commonly analyzed genes, such as BRCA1/BRCA2.

• Tier 2 Molecular Pathology CPT Codes – Used for less common genetic markers and panel-based tests.

• Proprietary Laboratory Analyses (PLA) Codes – Lab-specific genetic tests used by individual providers.

• Genomic Sequencing Procedure (GSP) Codes – Codes assigned to next-generation sequencing (NGS) and panel-based genomic testing.

Each year, the CPT code set is updated to reflect advancements in medical services. The 2025 CPT code update includes new codes for genetic and molecular testing, particularly in:

• Proprietary Laboratory Analyses (PLA) Codes
• Molecular Diagnostics
• Hereditary Testing 

These updates help healthcare providers bill correctly for genetic testing services, ensuring faster reimbursements and fewer claim denials.

Scenario: Handling Genetic Test Claim Denials A clinic submits a genetic test claim using an outdated CPT code, leading to a denial from the payer. The billing team reviews the updated 2025 CPT codes, resubmits the claim with proper documentation, and successfully secures reimbursement. Lesson: Always verify new CPT codes before submitting claims to avoid revenue loss.

2025 Optimized CPT Coding Guide for Molecular Pathology

The American Medical Association (AMA) has introduced 420 updates to the CPT code set, including 270 new codes, 112 deletions, and 38 revisions. Notably, 37% of the new codes pertain to proprietary laboratory analyses, primarily focusing on novel genetic testing.

Code	Description
81105	HPA-1 genotyping
81106	HPA-2 genotyping
81107	HPA-3 genotyping
81108	HPA-4 genotyping
81109	HPA-5 genotyping
81110	HPA-6 genotyping
81111	HPA-9 genotyping
81112	HPA-15 genotyping
81120	IDH1 common variants
81121	IDH2 common variants
81161	DMD duplication/deletion analysis
81162	BRCA1 & BRCA2 full sequencing and del/dup analysis
81163	BRCA1 & BRCA2 full sequencing analysis
81164	BRCA1 & BRCA2 full del/dup analysis
81165	BRCA1 full sequencing analysis
81166	BRCA1 full del/dup analysis
81167	BRCA2 full del/dup analysis
81168	CCND1/IGH translocation analysis
81170	ABL1 gene analysis
81171	AFF2 gene analysis for abnormal alleles
81172	AFF2 gene analysis for allele characterization
81173	AR gene full sequencing
81174	AR gene known familial variant analysis
81175	ASXL1 full gene sequencing
81176	ASXL1 targeted sequencing analysis
81177	ATN1 gene analysis for abnormal alleles
81178	ATXN1 gene analysis for abnormal alleles
81179	ATXN2 gene analysis for abnormal alleles
81180	ATXN3 gene analysis for abnormal alleles
81181	ATXN7 gene analysis for abnormal alleles
81182	ATXN8OS gene analysis for abnormal alleles
81183	ATXN10 gene analysis for abnormal alleles
81184	CACNA1A gene analysis for abnormal alleles
81185	CACNA1A full gene sequencing
81186	CACNA1A gene known familial variant analysis
81187	CNBP gene analysis for abnormal alleles
81188	CSTB gene analysis for abnormal alleles
81189	CSTB full gene sequencing
81190	CSTB known familial variant analysis
81191	NTRK1 translocation analysis
81192	NTRK2 translocation analysis
81193	NTRK3 translocation analysis
81194	NTRK translocation analysis
81195	Cytogenomic genome-wide analysis for hematologic malignancies
81200	BCR/ABL1 translocation analysis
81201	BCR/ABL1 translocation analysis, minor breakpoint
81202	BCR/ABL1 translocation analysis, other breakpoint
81203	BRAF gene analysis, V600 variants
81204	EGFR gene analysis, common variants
81205	EGFR gene analysis, T790M variant
81206	EGFR gene analysis, resistance variants
81207	EGFR gene analysis, uncommon variants
81208	FLT3 gene analysis, common variants
81209	JAK2 gene analysis, V617F variant
81210	JAK2 gene analysis, other variants
81218	KRAS gene analysis, common variants
81219	KRAS gene analysis, other variants
81225	NPM1 gene analysis, common variants
81226	NRAS gene analysis, common variants
81230	RUNX1 gene full sequencing analysis
81231	RUNX1 gene targeted sequencing analysis
81235	TERT gene analysis
81240	TP53 gene full sequencing analysis
81241	TP53 gene known familial variant analysis
81250	UGT1A1 gene analysis
81255	VKORC1 gene analysis
81256	CYP2C19 gene analysis
81257	CYP2D6 gene analysis
81258	CYP2C9 gene analysis
81259	CYP2C cluster gene analysis
81265	HFE gene analysis for common variants
81266	HFE gene analysis for known familial variant
81267	HLA class I typing
81268	HLA class II typing
81270	HLA-B*5701 allele analysis
81272	HLA-DQB1 typing
81275	HLA-DRB1 typing
81280	CFTR gene analysis, common variants
81281	CFTR gene analysis, known familial variant
81282	CFTR gene full sequencing analysis
81283	CFTR gene del/dup analysis
81290	MGMT gene analysis
81291	MLH1 gene analysis, common variants
81292	MLH1 gene full sequencing
81293	MLH1 gene known familial variant
81294	MLH1 gene del/dup analysis
81295	MSH2 gene full sequencing
81296	MSH2 gene known familial variant
81297	MSH2 gene del/dup analysis
81298	MSH6 gene full sequencing
81299	MSH6 gene known familial variant
81300	MSH6 gene del/dup analysis
81301	PMS2 gene full sequencing
81302	PMS2 gene known familial variant
81303	PMS2 gene del/dup analysis
81310	NTRK fusion analysis

Billing Guidelines for Medicare Coverage and Molecular Pathology Procedures

The 2025 CPT coding updates include modifications in molecular testing, sequencing, and risk assessment. Below is a breakdown:

Medicare Billing for Non-Covered Services

It is improper to bill Medicare for non-covered services as if they are covered. When submitting claims for services that are not eligible for coverage, ensure the correct modifier is applied.

Gene-Specific Code Selection

Code selection depends on the specific gene (s) being analyzed. Codes for gene variant testing use common variant names. While the listed variants are typically included in the test, this list is not exhaustive. Any additional variants of the same gene included in the analysis are part of the procedure and should not be reported separately.

Full gene sequencing should not be reported using variant-specific codes unless the CPT code explicitly includes “full gene sequence” in its description.

Tier 1 and Tier 2 Molecular Pathology Codes

• Tier 1 codes apply to tests for a specific gene or Human Leukocyte Antigen (HLA) locus.
• Tier 2 codes (81400-81408) cover molecular pathology procedures not listed in Tier 1 and typically represent lower-volume or rare disease testing. These codes should be used only when necessary and as specified in coding and billing policies.

If a claim includes the following Tier 2 codes, additional details must be provided in the claim narrative to specify the gene(s) analyzed. Otherwise, the claim may be rejected:

• 81400
• 81401
• 81402
• 81403
• 81404
• 81405
• 81406
• 81407
• 81408
• 81479 (Unlisted Molecular Pathology)

Reporting Unlisted Molecular Pathology Code (81479)

Providers must use the procedure code that best describes the performed service. If no Tier 1 or Tier 2 code appropriately represents the analyte tested, the unlisted molecular pathology code (81479) should be used.

When billing 81479, the gene being tested must be specified in:

• Block 80 (Part A for UB-04 claims)
• Box 19 (Part B for paper claims)
• Electronic equivalent fields for digital claims

Failure to include this information will result in claims being returned or denied. Medical records may also be requested to verify the procedure’s analytic validity, clinical utility, and justification for using 81479.

Documentation for Multiple Procedure Codes

If multiple procedure codes are submitted on a claim (whether standard or unlisted), documentation must clearly support each code. If the documentation does not correspond with the billed codes, the services may be denied under Title XVIII of the Social Security Act, Section 1833.

Testing for Multiple Genes & Next-Generation Sequencing (NGS)

Testing a panel of genes differs from testing individual genes separately. Claims must be medically justified:

• If billing for a panel, medical records must support its necessity.
• If billing for individual genes, each must be justified as necessary in the patient’s record.

Genes tested on the same date of service are categorized as:

• Parallel Testing: When multiple genes are analyzed at the same time for the same indication without one result influencing another.
• Serial Testing: When gene analysis is done in sequence, with later tests depending on earlier results.

If NGS technology is used and multiple genes are tested in parallel, they are considered part of a single panel, in alignment with the NCCI Manual (Chapter 10, Section F, Number 8). If genes are tested in a serial manner, claims should be submitted individually for each gene. The treating clinician’s order must reflect whether they requested a panel or individual genes, and records should support the medical necessity of the service billed.

Medicare policy does not allow separate payment for different testing methods applied to the same analyte.

Billing multiple distinct genetic tests for a single patient on the same date is generally not expected. In rare cases where more than one test is medically necessary, providers must confirm each as a separate procedural service using modifier -59.

Modifier -59: Distinct Procedural Service

Modifier -59 is used to indicate that a procedure is independent from others performed on the same day, applying to radiology, surgical, or medical services when appropriate.

Billing rules for Modifier -59:

• The first reported code is billed without a modifier.
• Additional codes are billed on separate lines with the modifier.
• Documentation must support a different session, procedure, site, system, incision, lesion, or injury from other services performed on the same day.

If another, more specific modifier is available, it should be used instead of -59. Using this modifier signifies that a service is distinct rather than part of a panel and may trigger a request for medical records. Frequent use of modifier -59 may lead to medical review.

Genomic Sequencing Profiles (GSP)

When a genomic sequencing test includes genes listed under multiple code descriptors, the most specific code for the primary disorder should be reported. Submitting multiple codes for the same gene will result in claim rejection or denial.

Multianalyte Assays with Algorithmic Analyses (MAAAs) & Proprietary Laboratory Analyses (PLAs)

If a valid PLA code exists, it must be used instead of a Tier 1 or Tier 2 code. Submitting both a PLA and a Tier 1/Tier 2 code is considered incorrect coding and may result in claim denial.

MAAA component procedures should not be billed separately. Claims that report additional codes for MAAA inputs will be denied.

• PLA and MAAA codes are listed in Appendix O of the CPT Manual.
• If no specific code exists, the unlisted MAAA procedure code (81599) should be used.
• When billing 81599, a brief (under 80 characters) description of the analysis must be included in:
  • Block 80 (Part A UB-04 claims)
  • Box 19 (Part B paper claims)
  • The electronic equivalent field for digital claims

Claims missing this information will be returned or denied. Medical records may also be requested to verify the test’s validity and necessity.

Date of Service (DOS)

For clinical laboratory tests and pathology services, the DOS is typically the date the specimen was collected. If collection spans two calendar days, the DOS is the date collection ended. Exceptions to DOS policies exist, as outlined in CMS IOM Publication 100-04, Chapter 16, Section 40.8.

Documentation Requirements

All medical records must be:

• Legible and include patient identification details (name, DOS, etc.)
• Signed by the responsible physician or non-physician practitioner (NPP)
• Supportive of the reported ICD-10-CM and CPT/HCPCS codes

Per CFR Section 410.32, the medical record must demonstrate that testing influences treatment and is necessary for managing the patient’s condition.

Ordering physician/NPP documentation must include:

• Relevant history, physical exam findings, and diagnostic rationale
• Evidence of at least two E/M visits within the last six months
• Test orders that clearly specify the requested analyses

Performing laboratories must maintain records including:

• Accreditation status
• Test requisition forms
• Procedure records
• Quality control documentation

Failure to provide adequate documentation may result in claim denials or requests for additional records.

The Bottom Line

The 2025 CPT code updates for genetic testing introduce new billing opportunities and challenges for healthcare providers and laboratories. Keeping up with molecular pathology, genomic sequencing, and proprietary test codes is crucial for ensuring accurate reimbursement. Understanding payer policies, compliance requirements, and billing best practices will help streamline claims and prevent revenue loss. For a smooth transition, it’s recommended to consult coding experts and medical billing professionals who specialize in genetic testing reimbursement.

References: 

https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleid=58917 https://www.ama-assn.org/press-center/press-releases/ama-releases-cpt-2025-code-set