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HLA genes are highly polymorphic and structurally complex. They are located in the major histocompatibility complex (MHC) on chromosome 6, and the frequency of alleles and haplotypes varies widely among human populations.  In this paper, we calculated the allele and haplotype frequencies using the HLA data of more than 120 000 Italian unrelated bone marrow donors enrolled in the national registry (IBMDR) and typed them with a high‐resolution (HR) method for the HLA‐A, ‐B, ‐C and ‐DRB1 alleles. The allele frequency data were obtained by manual counting; haplotype frequencies were calculated using the expectation maximisation (EM) algorithm. The total numbers of observed alleles were 226 for HLA‐A, 343 for HLA‐B, 201 for HLA‐C and 210 for HLA‐DRB1, which account for 5.4%, 6.7%, 5.2% and 8.5%, respectively, of each locus allele (IPD‐IMGT/HLA Database Release 3.32, April 2018). The three most frequent Italian haplotypes were  HLA‐A*01:01 ~ B*08:01 ~ C*07:01 ~ DRB1*03:01  (2.5%),  A*02:01 ~ B*18:01 ~C*07:01~ DRB1*11:04  (1.1%)  and A*30:01 ~ B*13:02 ~ C*06:02 ~ DRB1*07:01  (1.1%). Moreover, for a relevant subset of the examined population (>100 000 individuals), the birthplace was available, and thus, we grouped the frequency data based on the corresponding Italian geographic areas, describing the HLA specificity of the Italian regional populations. The haplotype frequencies were also compared between national and regional data, and we observed remarkable differences in the regional haplotype frequencies, particularly in Sardinia. This study represents a valid tool to identify a more efficient haematopoietic stem cell unrelated donor recruitment and selection strategy, as well as for population genetic and HLA‐disease association fields.

High‐resolution analysis of the HLA‐A, ‐B, ‐C and ‐DRB1 alleles and national and regional haplotype frequencies based on 120 926 volunteers from the Italian Bone Marrow Donor Registry