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

CPT code 81378 denotes a high-resolution molecular laboratory assay for human leukocyte antigen (HLA) genes, covering HLA Class I (A, B, C) and Class II (DRB1). This detailed genotyping is clinically important for transplant matching, immunogenetics, and certain diagnostic contexts where precise HLA characterization affects clinical decisions. Nationally, accurate HLA typing supports organ and stem cell transplantation programs and informs precision immunology care pathways.

Key payers addressed in this summary include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the code’s clinical scope, typical service setting, and what to expect in payer coverage discussions. The publication outlines common billing and documentation themes relevant to molecular laboratory services, highlights benchmarking topics used by payers, and summarizes policy and reimbursement considerations that commonly affect HLA molecular testing nationwide.

This resource is intended to orient laboratory managers, billing professionals, and policy analysts to the clinical context, payer landscape, and operational considerations tied to CPT code 81378, enabling informed engagement with payers and institutional stakeholders about HLA high-resolution testing.

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Billing Code Overview

CPT code 81378 describes a high-resolution molecular laboratory test that assesses human leukocyte antigen (HLA) genes for Classes I and II. For this service, HLA Class I includes HLA–A, HLA–B, and HLA–C, and HLA Class II for this test includes HLA–DRB1.

Service type: Technical molecular laboratory testing for high-resolution HLA typing.

Typical site of service: Clinical diagnostic laboratory or reference molecular laboratory.

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

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Billing Code Overview

Service type: Technical molecular laboratory testing for high-resolution HLA typing.

Typical site of service: Clinical diagnostic laboratory or reference molecular laboratory.

Clinical & Coding Specifications

Clinical Context

A patient being evaluated for organ transplantation compatibility or for investigation of suspected immune-mediated disease is referred for high-resolution HLA typing. Typical patients include potential kidney, liver, pancreas, or bone marrow transplant recipients and donors, and patients undergoing workup for recurrent pregnancy loss or suspected antibody‑mediated disease. The clinical workflow begins with collection of a peripheral blood specimen (EDTA tube) from the patient or donor in an outpatient clinic, transplant center, or hospital. The specimen is sent to a molecular diagnostics laboratory where DNA is extracted and amplified. The lab analyst performs high-resolution assessment of HLA Class I loci (HLA‑A, HLA‑B, HLA‑C) and HLA Class II locus (HLA‑DRB1) using sequence‑based typing or next‑generation sequencing methods. Results are reported as allelic-level HLA types used by transplant teams, histocompatibility labs, and immunology clinics to determine donor‑recipient compatibility, sensitization risk, and to guide immunosuppressive planning. Typical site of service: outpatient clinic, hospital inpatient, or independent molecular diagnostics laboratory performing technical testing.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	When reporting the physician or laboratory director interpretation/analysis separate from the technical testing if applicable
`TC`	Technical component	When billing only the technical component of the molecular test performed by the lab
`90`	Reference (outside) laboratory	When the performed test is sent to an outside/reference laboratory for analysis
`91`	Repeat clinical diagnostic laboratory test	When the test is repeated on the same day and the repeat is clinically necessary
`59`	Distinct procedural service	When another distinct unrelated procedure is performed on the same day that should be reported separately
`52`	Reduced services	When the test is partially reduced or not performed to full extent
`53`	Discontinued procedure	If testing was started but discontinued for clinical reasons before completion
`22`	Increased procedural services	Rarely used if test complexity or time far exceeds typical and payor allows an increased payment modifier
`90`	(duplicate intentionally omitted in practice)	(Use only once in claims)
`91`	(duplicate intentionally omitted in practice)	(Use only once in claims)

Taxonomy Code	Specialty	Notes
2080P0200X	Clinical Molecular Biology Laboratory	Specialists performing molecular HLA typing and sequencing
207L00000X	Clinical Laboratory	Clinical laboratory specialists overseeing technical testing workflows
208M00000X	Pathology	Pathologists who interpret and sign molecular diagnostic reports
3336C0002X	Transplant Immunology	Laboratory or clinical specialists focused on histocompatibility testing
207K00000X	Hematology & Oncology	Hematologists involved in stem cell transplant donor matching

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z48.21`	Encounter for aftercare following kidney transplant	Used when HLA typing is part of pre‑ or post‑transplant compatibility and follow‑up
`Z94.0`	Kidney transplant status	Indicates presence of transplant where HLA matching and monitoring are relevant
`Z33.1`	Pregnant state, incidental	HLA typing may be used in recurrent pregnancy loss related workups (maternal‑fetal incompatibility assessments)
`D47.1`	Chronic myeloproliferative disease	Patients being evaluated for hematopoietic stem cell transplant require HLA high‑resolution typing
`Z48.21`	(duplicate for other solid organ transplant aftercare)	Used similarly for other organ transplant evaluations
`Z52.1`	Bone marrow transplant status	Indicates need for donor‑recipient HLA compatibility testing
`O26.82`	Pregnancy care for other specified conditions, antepartum	Used when recurrent pregnancy loss or alloimmune concerns prompt HLA testing

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88360`	Interpretation and report of morphologic and molecular pathology procedures	May be billed when a pathologist performs a separate interpretive report related to the molecular findings
`0018U`	HLA typing, sequence‑based; multi‑locus, high‑resolution (example proprietary panel)	Alternative or companion high‑resolution HLA tests sometimes used in parallel or for extended typing
`83891`	Molecular biology procedure, DNA extraction and purification	Commonly performed as a preparatory technical step before sequence‑based HLA typing
`81479`	Unlisted molecular pathology procedure	Used when no specific CPT exists for a novel or proprietary HLA assay component
`81025`	Urinalysis non‑automated, microscopic only	Example of ancillary testing in transplant evaluation workflows (pre‑op)

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

CPT 81379: High-Resolution HLA Class I Typing

CPT-81380-HLA-HIGH-RESOLUTION-CLASS-I-TYPING

CPT 81380: High-Resolution HLA Class I Molecular 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	When reporting the physician or laboratory director interpretation/analysis separate from the technical testing if applicable
`TC`	Technical component	When billing only the technical component of the molecular test performed by the lab
`90`	Reference (outside) laboratory	When the performed test is sent to an outside/reference laboratory for analysis
`91`	Repeat clinical diagnostic laboratory test	When the test is repeated on the same day and the repeat is clinically necessary
`59`	Distinct procedural service	When another distinct unrelated procedure is performed on the same day that should be reported separately
`52`	Reduced services	When the test is partially reduced or not performed to full extent
`53`	Discontinued procedure	If testing was started but discontinued for clinical reasons before completion
`22`	Increased procedural services	Rarely used if test complexity or time far exceeds typical and payor allows an increased payment modifier
`90`	(duplicate intentionally omitted in practice)	(Use only once in claims)
`91`	(duplicate intentionally omitted in practice)	(Use only once in claims)

Taxonomy Code	Specialty	Notes
2080P0200X	Clinical Molecular Biology Laboratory	Specialists performing molecular HLA typing and sequencing
207L00000X	Clinical Laboratory	Clinical laboratory specialists overseeing technical testing workflows
208M00000X	Pathology	Pathologists who interpret and sign molecular diagnostic reports
3336C0002X	Transplant Immunology	Laboratory or clinical specialists focused on histocompatibility testing
207K00000X	Hematology & Oncology	Hematologists involved in stem cell transplant donor matching

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z48.21`	Encounter for aftercare following kidney transplant	Used when HLA typing is part of pre‑ or post‑transplant compatibility and follow‑up
`Z94.0`	Kidney transplant status	Indicates presence of transplant where HLA matching and monitoring are relevant
`Z33.1`	Pregnant state, incidental	HLA typing may be used in recurrent pregnancy loss related workups (maternal‑fetal incompatibility assessments)
`D47.1`	Chronic myeloproliferative disease	Patients being evaluated for hematopoietic stem cell transplant require HLA high‑resolution typing
`Z48.21`	(duplicate for other solid organ transplant aftercare)	Used similarly for other organ transplant evaluations
`Z52.1`	Bone marrow transplant status	Indicates need for donor‑recipient HLA compatibility testing
`O26.82`	Pregnancy care for other specified conditions, antepartum	Used when recurrent pregnancy loss or alloimmune concerns prompt HLA testing

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`88360`	Interpretation and report of morphologic and molecular pathology procedures	May be billed when a pathologist performs a separate interpretive report related to the molecular findings
`0018U`	HLA typing, sequence‑based; multi‑locus, high‑resolution (example proprietary panel)	Alternative or companion high‑resolution HLA tests sometimes used in parallel or for extended typing
`83891`	Molecular biology procedure, DNA extraction and purification	Commonly performed as a preparatory technical step before sequence‑based HLA typing
`81479`	Unlisted molecular pathology procedure	Used when no specific CPT exists for a novel or proprietary HLA assay component
`81025`	Urinalysis non‑automated, microscopic only	Example of ancillary testing in transplant evaluation workflows (pre‑op)

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

CPT 81379: High-Resolution HLA Class I Typing

CPT-81380-HLA-HIGH-RESOLUTION-CLASS-I-TYPING

CPT 81380: High-Resolution HLA Class I Molecular 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 81378: High-Resolution HLA Class I and II Molecular Typing

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Billing Code Overview

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

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

Sign up for cpt 81378 policy alerts

Billing Code Overview

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

Sign up for cpt 81378 policy alerts

Billing Code Overview

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 81378 cover and where is it typically performed?

Which modifiers are commonly used when billing CPT 81378?

What related CPT codes might appear with or near CPT 81378 on claims?

For which clinical scenarios and diagnosis codes is CPT 81378 commonly used?

Which payers are mentioned and does the page provide specific reimbursement rates or policy details?

References

Clinical & Coding Specifications

Clinical Context

Coding Specifications

Related Diagnoses

Related CPT Codes

Related Codes

What does CPT 81378 cover and where is it typically performed?

Which modifiers are commonly used when billing CPT 81378?

What related CPT codes might appear with or near CPT 81378 on claims?

For which clinical scenarios and diagnosis codes is CPT 81378 commonly used?

Which payers are mentioned and does the page provide specific reimbursement rates or policy details?

References