Uros population from the Titikaka Lake live in about 42 floating reed (‘totora’) islands in front of Puno City (Peru) at a 4000 m high altiplano. They present both an mtDNA and a human leucocyte antigen (HLA) profile different from the surrounding populations: mtDNA A2 haplogroup is common to Uros and Amazon forest lowland Amerindians. HLA genetic distances between populations have been calculated and neighbour-joining dendrograms and correspondence analyses were carried out. Approximately 15 006 HLA chromosomes from worldwide populations have been used for comparisons. Only eight HLA-A alleles have been found, three of them accounting for most of the frequencies. The same phenomenon is seen for HLA-B, HLA-DRB1 and HLA-DQB1 alleles: a few alleles (3, 4 and 3, respectively) are present in most individuals. The presence of HLA-B*4801 and HLA-DRB1*0901 alleles in a relatively high frequency (although not the most frequent alleles found) is a characteristic shared with Asians and some populations from the Andean altiplano. Three specific Uros haplotypes have been found among the most frequent ones: HLA-A*680102-B*3505-DRB1*0403-DQB1*0302; HLA-A*2402-B*1504-DRB1*1402-DQB1*0301; and HLA-A*2402-B*4801-DRB1*0403-DQB1*0302. The present study suggests that Uros may have been one of the first populations from the shores of the Titikaka Lake coming from the Amazonian forest, which might have given rise to other later differentiated ethnic group (i.e. Aymaras). Uros HLA profile is also useful to study genetic epidemiology of diseases linked to HLA and to construct a future transplant waiting list by adding up regional lists in order to get a bigger pool for transplanting with better HLA matching.