Aim: To compare the Amerindians HLA allele frequencies with those of other First American Natives and also those of other worldwide populations in order to clarify the still unclear peopling of the Americas and the origins of Amerindians. Subjects and methods: All possible HLA data already obtained about early Native American populations are used. Genetic distances and N-J dendrogram method are applied. Results and conclusions: Results and discussion have given to the following conclusions: 1) Pacific Ocean boat trips may have contributed to the HLA genetic American profile (or vice versa); 2) North West Canadian Athabaskans have had gene flow with close neighboring populations, Amerindians, Pacific Islanders including East Australians, and Siberians; 3) Amerindians entrance to America may have been different to that of Athabaskans, Aleuts and Eskimos; Amerindians may have been in their lands long before Athabaskans and Eskimos because they present and altogether different set of HLA-DRB1 allele frequencies; 4) Amerindians show very few ―particular‖ single-locus alleles, but have unique extended haplotypes; 5) Our results do not support the three-wave model of American peopling, but another model where the Pacific Coast is also an entrance point. Reverse migration (America to Asia) is not discarded and different movements of people in either direction in different times are supported by the Athabaskan population admixture with Asian-Pacific population and with Amerindians. Key words: Aleuts, Amerindians, Athabaskans, Eskimo, HLA, peopling of America.