We describe for the first time the high‐resolution profiling of HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1 and ‐DPB1 in a culturally and geographically distinct Mexican ethnic group, the Tarahumaras. The alleles most frequently found by reference strand‐mediated conformational analysis in this population were for class I: HLA‐A*240201, *020101/09, *0206, *310102, *680102; HLA‐B*4002, *1501, *510201, *3501/02/03, *4005, *4801; HLA‐Cw*0304, *0801, *0102, *040101; and for class II: HLA‐DRB1*080201, *1402, *040701; HLA‐DQB1*0402, *0301, *0302/07; HLA‐DPB1*0402, *0401, *020102. In addition, a novel allele, HLA‐A*0257, was found. Based on comparison of presently known HLA‐DRB1 and ‐DQB1 allele frequencies in Amerindian groups and worldwide populations, the Tarahumaras are unexpectedly more related to the geographically and linguistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes.