In comparison to South America, native North Americans tend to be less diverse in their repertoire of HLA class I alleles. Based upon this observation, we hypothesized that the Yupik Eskimo would exhibit a limited number of previously identified class I HLA alleles. To test this hypothesis, sequence-based typing was performed at the HLA-A, -B and -C loci for 99 Central Yupik individuals from southwestern Alaska. Two new class I alleles, A*2423 and Cw*0806, were identified. While A*2423 was observed in only one sample, Cw*0806 was present in 26 of the 99 individuals and all of the Cw*0806 samples contained B*4801. Allele Cw*0806 differs from Cw*0803 by a single nucleotide substitution such that Cw*0803 may be the progenitor of Cw*0806. Allele Cw*0803 was originally characterized as unique to South America, but detection of Cw*0803 in the Yupik indicates that Cw*0803 was a founding allele of the Americas. The presence of new alleles and previously unrecognized founding alleles in the Yupik population show that natives of North America are more diverse than previously envisioned.