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CPT 81380: High-Resolution HLA Class I Molecular Typing

CPT code 81380 represents a high-resolution molecular assay for human leukocyte antigen (HLA) genes focused on a single Class I locus. This test is clinically important for organ and stem cell transplantation compatibility, donor matching, and detailed immunogenetic assessment. Accurate HLA typing at high resolution can influence transplant outcomes and patient selection for immunologically sensitive therapies, making it a nationally relevant laboratory service.

Key payers covered in this overview include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise explanation of the clinical purpose and laboratory setting for CPT code 81380, along with coverage and billing considerations relevant to major national payers. The publication summarizes common modifiers and administrative elements associated with laboratory molecular testing, highlights typical sites of service, and outlines what types of benchmarks and policy updates to expect in related payer guidance. Where specific input data is unavailable, the report notes that those items are not provided.

The content is organized to help billing managers, laboratory directors, and policy analysts understand service definition, payer relevance, and the administrative context for high-resolution HLA Class I molecular testing under CPT code 81380. Data not available in the input are identified as such.

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Billing Code Overview

CPT code 81380 describes a high-resolution molecular test for human leukocyte antigen (HLA) genes, performed for one Class I locus. The procedure involves laboratory molecular techniques to determine HLA variants at high resolution for clinical purposes such as transplant compatibility and immunogenetic evaluation.

Service type: Clinical molecular laboratory testing (HLA typing, high-resolution)

Typical site of service: Clinical laboratory or hospital-based molecular diagnostics laboratory

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CPT 81380: High-Resolution HLA Class I Molecular Typing

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Billing Code Overview

Service type: Clinical molecular laboratory testing (HLA typing, high-resolution)

Typical site of service: Clinical laboratory or hospital-based molecular diagnostics laboratory

Clinical & Coding Specifications

Clinical Context

A 32-year-old patient undergoing evaluation as a potential organ (kidney) or marrow transplant donor/recipient is referred for high-resolution human leukocyte antigen (HLA) typing of a single Class I locus. The specimen (blood or buccal swab) is collected in the outpatient phlebotomy lab or transplant clinic and routed to the molecular diagnostic laboratory. A clinical laboratory scientist performs a molecular assay (e.g., sequence-based typing or next-generation sequencing) to determine high-resolution alleles for the specified Class I locus (HLA-A, HLA-B, or HLA-C). Results are reviewed by the laboratory director and reported to the transplant team or ordering provider to inform donor-recipient matching, immunogenetic risk assessment, or immune compatibility decisions. Typical sites of service include hospital outpatient laboratory, independent clinical laboratory, or specialized transplant center laboratory.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the professional (interpretive) component of a divided lab service if applicable to the reporting laboratory.
`TC`	Technical component	Use when billing only the technical component (assay performance) of the test performed by the laboratory.
`90`	Reference (outside) laboratory	Use when the performing laboratory bills on behalf of or as an outside reference lab.
`91`	Repeat clinical diagnostic lab test	Use when an exact repeat of the same HLA assay is performed on the same day for verification.
`59`	Distinct procedural service	Use when another distinct and separate service is performed on the same day that is not typically bundled.
`52`	Reduced services	Use if the assay was partially performed or limited compared with the full test.
`53`	Discontinued procedure	Use when testing was started but discontinued for patient-related or specimen issues.
`22`	Increased procedural services	Use when the test required substantially greater resources or complexity than typical.
`78`	Unplanned return to the operating/procedure room	Rarely applicable; use only if an invasive specimen collection or operative procedure required an unplanned return related to the test.
`59`	Distinct procedural service	Use when the HLA assay is separately reportable and not included in another service on the claim.

Taxonomy Code	Specialty	Notes
207RG0100X	Clinical Molecular Genetics Laboratory	Laboratory specialists performing molecular HLA testing.
207RA0000X	Pathology	Anatomic and clinical pathologists who direct molecular diagnostic services.
208D00000X	Clinical Laboratory	Clinical laboratory directors and medical technologists overseeing testing.
207L00000X	Infectious Disease (Laboratory Molecular)	Specialists involved when HLA testing is part of transplant infectious disease workup.
2084P0800X	Transplant Surgeon	Ordering clinicians in transplant programs coordinating HLA testing.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z48.21`	Encounter for aftercare following organ transplant	Used for post-transplant compatibility monitoring and follow-up HLA testing.
`Z48.22`	Encounter for aftercare following bone marrow transplant	Relevant for donor-recipient matching and post-transplant chimerism assessments.
`Z52.4`	Donor of organ	Used when testing a living organ donor for HLA compatibility.
`Z52.0`	Bone marrow donor	Used for HLA typing of potential hematopoietic stem cell donors.
`Z31.84`	Encounter for genetic counseling related to reproductive carrier screening	Applicable when HLA results are part of broader genetic counseling in transplant planning.
`D47.Z9`	Hematologic neoplasm, unspecified	Used when HLA typing is required as part of transplantation planning for hematologic malignancies.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81381`	HLA typing, high resolution; each additional Class I locus (e.g., second locus)	Performed when more than one Class I locus requires high-resolution typing in a donor/recipient pair; billed in addition to the primary locus code.
`81383`	HLA typing, high resolution; Class II locus (e.g., HLA-DRB1)	Used when Class II high-resolution typing is required alongside Class I typing for comprehensive matching.
`81225`	HLA-B*57:01 allele testing via molecular technique	Performed when allele-specific testing for drug hypersensitivity is needed in addition to broad HLA typing.
`86399`	Unlisted immunology procedure	Rarely used if an atypical or novel HLA-related assay lacks an established code; used with caution and documentation.
`99000`	Technical courier/transportation for specimen	Applied when special courier services are required to transport specimens to reference laboratories for HLA testing.

CPT 81370: HLA Class I and II Low/Intermediate-Resolution Molecular Typing

CPT-81371-HLA-A-B-DRB1-LOW-INTERMEDIATE-RESOLUTION-TYPING

CPT 81371: HLA-A, HLA-B, HLA-DRB1 Low/Intermediate Resolution Typing

CPT-81372-HLA-CLASS-I-LOW-INTERMEDIATE-RESOLUTION-TYPING

CPT 81372: HLA Class I Low/Intermediate-Resolution Molecular Typing

CPT-81373-HLA-CLASS-I-LOW-INTERMEDIATE-RESOLUTION

CPT 81373: HLA Class I Low/Intermediate Resolution Molecular Test

CPT-81374-HLA-CLASS-I-LOW-INTERMEDIATE-RESOLUTION

CPT 81374: HLA Class I Low/Intermediate-Resolution Testing

CPT-81375-HLA-CLASS-II-LOW-INTERMEDIATE-RESOLUTION-TYPING

CPT 81375: HLA Class II Low/Intermediate-Resolution Molecular Typing

CPT-81376-HLA-CLASS-II-TYPING-LOW-INTERMEDIATE-RESOLUTION-TECHNICAL

CPT 81376: HLA Class II Typing, Low/Intermediate-Resolution Technical

CPT-81377-HLA-CLASS-II-ALLELE-GROUP-TYPING-LOW-INTERMEDIATE-RESOLUTION

CPT 81377: HLA Class II Allele Group Typing, Low/Intermediate Resolution

CPT-81378-HLA-HIGH-RESOLUTION-MOLECULAR-TYPING-CLASS-I-II-DRB1

CPT 81378: High-Resolution HLA Class I and II Molecular Typing

CPT-81379-HLA-CLASS-I-HIGH-RESOLUTION-TYPING

CPT 81379: High-Resolution HLA Class I Typing

Showing 1–10 of 13

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Jul 29, 2026.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Jul 29, 2026.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Jul 29, 2026.

Published by

Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when billing only the professional (interpretive) component of a divided lab service if applicable to the reporting laboratory.
`TC`	Technical component	Use when billing only the technical component (assay performance) of the test performed by the laboratory.
`90`	Reference (outside) laboratory	Use when the performing laboratory bills on behalf of or as an outside reference lab.
`91`	Repeat clinical diagnostic lab test	Use when an exact repeat of the same HLA assay is performed on the same day for verification.
`59`	Distinct procedural service	Use when another distinct and separate service is performed on the same day that is not typically bundled.
`52`	Reduced services	Use if the assay was partially performed or limited compared with the full test.
`53`	Discontinued procedure	Use when testing was started but discontinued for patient-related or specimen issues.
`22`	Increased procedural services	Use when the test required substantially greater resources or complexity than typical.
`78`	Unplanned return to the operating/procedure room	Rarely applicable; use only if an invasive specimen collection or operative procedure required an unplanned return related to the test.
`59`	Distinct procedural service	Use when the HLA assay is separately reportable and not included in another service on the claim.

Taxonomy Code	Specialty	Notes
207RG0100X	Clinical Molecular Genetics Laboratory	Laboratory specialists performing molecular HLA testing.
207RA0000X	Pathology	Anatomic and clinical pathologists who direct molecular diagnostic services.
208D00000X	Clinical Laboratory	Clinical laboratory directors and medical technologists overseeing testing.
207L00000X	Infectious Disease (Laboratory Molecular)	Specialists involved when HLA testing is part of transplant infectious disease workup.
2084P0800X	Transplant Surgeon	Ordering clinicians in transplant programs coordinating HLA testing.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z48.21`	Encounter for aftercare following organ transplant	Used for post-transplant compatibility monitoring and follow-up HLA testing.
`Z48.22`	Encounter for aftercare following bone marrow transplant	Relevant for donor-recipient matching and post-transplant chimerism assessments.
`Z52.4`	Donor of organ	Used when testing a living organ donor for HLA compatibility.
`Z52.0`	Bone marrow donor	Used for HLA typing of potential hematopoietic stem cell donors.
`Z31.84`	Encounter for genetic counseling related to reproductive carrier screening	Applicable when HLA results are part of broader genetic counseling in transplant planning.
`D47.Z9`	Hematologic neoplasm, unspecified	Used when HLA typing is required as part of transplantation planning for hematologic malignancies.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81381`	HLA typing, high resolution; each additional Class I locus (e.g., second locus)	Performed when more than one Class I locus requires high-resolution typing in a donor/recipient pair; billed in addition to the primary locus code.
`81383`	HLA typing, high resolution; Class II locus (e.g., HLA-DRB1)	Used when Class II high-resolution typing is required alongside Class I typing for comprehensive matching.
`81225`	HLA-B*57:01 allele testing via molecular technique	Performed when allele-specific testing for drug hypersensitivity is needed in addition to broad HLA typing.
`86399`	Unlisted immunology procedure	Rarely used if an atypical or novel HLA-related assay lacks an established code; used with caution and documentation.
`99000`	Technical courier/transportation for specimen	Applied when special courier services are required to transport specimens to reference laboratories for HLA testing.

CPT 81370: HLA Class I and II Low/Intermediate-Resolution Molecular Typing

CPT-81371-HLA-A-B-DRB1-LOW-INTERMEDIATE-RESOLUTION-TYPING

CPT 81371: HLA-A, HLA-B, HLA-DRB1 Low/Intermediate Resolution Typing

CPT-81372-HLA-CLASS-I-LOW-INTERMEDIATE-RESOLUTION-TYPING

CPT 81372: HLA Class I Low/Intermediate-Resolution Molecular Typing

CPT-81373-HLA-CLASS-I-LOW-INTERMEDIATE-RESOLUTION

CPT 81373: HLA Class I Low/Intermediate Resolution Molecular Test

CPT-81374-HLA-CLASS-I-LOW-INTERMEDIATE-RESOLUTION

CPT 81374: HLA Class I Low/Intermediate-Resolution Testing

CPT-81375-HLA-CLASS-II-LOW-INTERMEDIATE-RESOLUTION-TYPING

CPT 81375: HLA Class II Low/Intermediate-Resolution Molecular Typing

CPT-81376-HLA-CLASS-II-TYPING-LOW-INTERMEDIATE-RESOLUTION-TECHNICAL

CPT 81376: HLA Class II Typing, Low/Intermediate-Resolution Technical

CPT-81377-HLA-CLASS-II-ALLELE-GROUP-TYPING-LOW-INTERMEDIATE-RESOLUTION

CPT 81377: HLA Class II Allele Group Typing, Low/Intermediate Resolution

CPT-81378-HLA-HIGH-RESOLUTION-MOLECULAR-TYPING-CLASS-I-II-DRB1

CPT 81378: High-Resolution HLA Class I and II Molecular Typing

CPT-81379-HLA-CLASS-I-HIGH-RESOLUTION-TYPING

CPT 81379: High-Resolution HLA Class I Typing

Showing 1–10 of 13

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Jul 29, 2026.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Jul 29, 2026.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Jul 29, 2026.

Published by

Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

OpenPayer

CPT 81380: High-Resolution HLA Class I Molecular Typing

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Billing Code Overview

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Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

References

CPT 81380: High-Resolution HLA Class I Molecular Typing

Sign up for cpt 81380 policy alerts

Billing Code Overview

CPT 81380: High-Resolution HLA Class I Molecular Typing

Sign up for cpt 81380 policy alerts

Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What clinical purpose and setting does CPT 81380 cover?

Which billing modifiers apply to CPT 81380 and when are they used?

What related CPT codes should be considered with 81380?

Which diagnosis codes are commonly associated with HLA high-resolution Class I typing?

Which payers are referenced for CPT 81380 and does the page provide reimbursement rates?

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What clinical purpose and setting does CPT 81380 cover?

Which billing modifiers apply to CPT 81380 and when are they used?

What related CPT codes should be considered with 81380?

Which diagnosis codes are commonly associated with HLA high-resolution Class I typing?

Which payers are referenced for CPT 81380 and does the page provide reimbursement rates?

References