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    v1.0.30
    OpenPayerBilling CodesHLA TypingCPT cpt-81378-hla-high-resolution-molecular-typing-class-i-ii-drb1
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    CPT 81378: High-Resolution HLA Class I and II Typing

    CPT code 81378 describes a high-resolution molecular laboratory test for human leukocyte antigen (HLA) genes, providing sequence-level typing for HLA Class I (HLA‑A, HLA‑B, HLA‑C) and HLA Class II (HLA‑DRB1) to determine patient HLA alleles for clinical uses such as transplant matching and immunogenetic evaluation; this service is a molecular pathology/genetics test performed as a technical laboratory procedure in a clinical laboratory or molecular diagnostics laboratory setting.

    For related coverage guidance, see recent payer policy updates: Oral Cancer Screening and Testing, RTM Testing for Alpha-1 Antitrypsin Deficiency, Cytochrome P450 Genotype-Guided Treatment Strategy Corporate Medical Policy.

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    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.

    Related CPT Codes

    CPT CodeDescriptionRelationship to This Procedure
    88360Interpretation and report of morphologic and molecular pathology proceduresMay be billed when a pathologist performs a separate interpretive report related to the molecular findings
    0018UHLA 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
    83891Molecular biology procedure, DNA extraction and purificationCommonly performed as a preparatory technical step before sequence‑based HLA typing
    81479Unlisted molecular pathology procedureUsed when no specific CPT exists for a novel or proprietary HLA assay component
    81025Urinalysis non‑automated, microscopic onlyExample of ancillary testing in transplant evaluation workflows (pre‑op)

    Related Modifiers

    7 rows

    ModifierDescriptionWhen to Use
    26Modifier 26 (Professional Component) identifies and bills only the professional portion of a split service — the physician’s interpretation, report, and medical judgment — when the technical…- Use CPT Modifier -26 when you are billing only the professional component (PC) of a split‑bill eligible service—i.e., you performed the physician interpretation, medical judgment and prepared a…
    90Modifier ‑90 (Reference/Outside Laboratory) indicates that a laboratory test was performed by an entity other than the treating or reporting provider. The American Medical Association defines…- Use CPT modifier -90 when a laboratory test is performed by an outside/reference laboratory (an entity other than the treating or reporting physician or qualified professional) and the claim needs…
    91Modifier 91 — “Repeat Clinical Diagnostic Laboratory Test” — is appended when the exact same CPT laboratory test is performed more than once for the same patient on the same day because serial,…- Use modifier 91 when the exact same CPT laboratory test is performed more than once on the same patient on the same date because serial or repeated testing is medically necessary to monitor…
    59Modifier 59 indicates a distinct procedural service when two procedures that are not normally billed together are clinically and procedurally separate. The CPT definition (as reiterated by CMS)…- Use modifier -59 to report a distinct procedural service when documentation supports that the procedure reported is not normally billed together with another service on the same day because of a…
    52Modifier ‑52 (Reduced Services) indicates that a service or procedure was partially reduced or omitted at the provider’s discretion, allowing reporting of the basic procedure number with a qualifier…- Use modifier -52 when a physician or qualified health professional electively reduces or omits part of a procedure or service (for example, performing fewer required views or omitting a portion of…
    53Modifier 53 (Discontinued Procedure) signals that a surgical or diagnostic service was begun by the physician but terminated because of extenuating circumstances that threatened the patient’s…- Use modifier -53 when a physician/qualified healthcare professional has started a surgical or diagnostic procedure (e.g., anesthesia administered, incision or scope insertion) and then discontinues…
    22Modifier –22 (Increased Procedural Services) is used when a reported procedure is substantially more extensive than normally required. The CPT Manual and CMS state it may be appended only when the…- When to use: Append modifier -22 to a procedural CPT code when the service performed is substantially more extensive than the usual service described by that code — i.e., the procedure required…

    Related Provider Taxonomies

    8 rows

    Taxonomy Code
    207L00000X
    208M00000X
    3336C0002X
    207K00000X
    133VN1006X
    253Z00000X
    103TE1000X
    282J00000X

    Related Payer Policy Updates

    Specialty: Genetic & Molecular Testing1 / 3

    10 rows

    PolicyPayerEffective Date
    Oral Cancer Screening and TestingOscar Health2027-01-01
    RTM Testing for Alpha-1 Antitrypsin DeficiencyOscar Health2027-01-01
    Cytochrome P450 Genotype-Guided Treatment Strategy Corporate Medical Policybcbsvermont2027-01-01
    Carrier Testing Panels for Genetic Diseases (for Kentucky Only)UnitedHealthcare2026-10-01
    Genetic Testing for Neurological Disorders (for Kansas Only)UnitedHealthcare2026-10-01
    Genetic and Molecular TestingProvidence Health Plan2026-10-01
    Cell-Free Fetal DNA Testing (for Idaho Only)UnitedHealthcare2026-10-01
    Next Generation Sequencing for Minimal Residual Disease DetectionProvidence Health Plan2026-10-01
    Pharmacogenetic Panel Testing (for Kansas Only)UnitedHealthcare2026-10-01
    Non-Covered Genetic Panel TestsProvidence Health Plan2026-10-01

    Related Codes

    CPT-81370-HLA-CLASS-I-II-LOW-INTERMEDIATE-RESOLUTION-TESTING

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

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

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

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

    CPT 81372: HLA Class I Low/Intermediate Resolution Typing

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

    CPT 81373: HLA Typing, Low or Intermediate Resolution, One Class I Locus

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

    CPT 81374: HLA Class I Allele Group Typing, Low/Intermediate Resolution

    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 Low/Intermediate Resolution, Technical Test

    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: HLA Class I High-Resolution Molecular Typing

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

    CPT 81380: HLA High-Resolution Molecular Typing, One Class I Locus

    Showing 1–10 of 13

    Frequently Asked Questions

    References

    1. 1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
    2. 2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
    3. 3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.
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