Aleuts have inhabited Aleutian Islands since about 9000 years BP according to fossil and genetic (mtDNA) records. They are genetically different to Eskimo, Amerindian and Na-Dene speakers according to their HLA profile; this correlates with cultural and anthropological Aleut distinctiveness. No typical Amerindian HLA alleles have been found in a significant frequency. Their HLA relatedness to Saami (or Lapps, northern Scandinavians), Finns and Pomors (North-West Russia) indicates an ancient possible origin from the Baikal Lake Area (southern Siberia) around the present day Buryat peopling area; other origins are not discarded. Aleuts characteristic HLA profile may influence future transplantation programs in the region and be useful to study diseases linked to HLA epidemiology.