The purpose of this study was to establish the frequencies ofCYP2D6,CYP1A1,GSTM1andp53polymorphic genotypes in Tundra Nentsi, which comprises the small group of indigenous people belonging to Northern Mongoloids and Caucasians of Western Siberia. A total number of 102 Tundra Nentsi individuals and 96 Caucasians of Western Siberia were genotyped by means of polymerase chain reaction-based assays. Mutated alleles comprisingCYP2D6*4,CYP1A1Val,GSTM1*0andp53Prowere analysed along with the wild-type alleles. The results showed the intermedial position ofCYP2D6*4allele frequency in Tundra Nentsi, compared to Caucasians and Orientals (0.07 versus 0.2,P= 0.0003; 0.07 versus 0.003,P= 1×10−6, respectively). Thus, our data indicate that the intermedial position of Tundra Nentsi between Orientals and Caucasians most likely shows the Caucasian ancestral origin ofCYP2D6*4allele. Comparative analysis ofp53Proallele frequency showed the pronounced ethnic differences with geographic gradient. Though the frequency ofp53Proallele ranged from 0.17 in Tundra Nentsi up to 0.3 in Caucasians of Western Siberia (P= 0.002), which is in agreement with the previously reported radial distribution of the known genetic markers. No differences were found in theCYP1A1Valallele distribution among Caucasians of Western Siberia and Caucasoid populations presented in other studies, whereas the frequency ofValallele in Nentsi was 1.5-fold higher (P= 0.076) compared to the Japanese group. It was found that the frequency ofGSTM1null genotype in Tundra Nentsi was only 39.8%. The frequency ofGSTM1null genotype in females was higher than in males (0.27 and 0.50, respectively) but that difference was not statistically significant. Comparative analyses of the distribution of putative markers towards cancer susceptibility,CYP1A1Val,GSTM1*0andp53Proalleles, have shown that the healthy Tundra Nentsi population (Northern Mongoloids) have a low number ofp53Proalleles andGSTM1*0/*0genotypes and a high level ofCYP1A1Valalleles. Further investigations of gene polymorphisms in isolated Northern native populations would be valuable in clarifying the origin of Northern natives. All this is important for comparative analyses of pharmacogenetic data in Mongoloid populations.