Genomic diversity of 21 STR loci has been studied in six ethnic populations of Daghestan (the Caucasus), namely, Avars, Dargins, Kubachians, Lezgins, and Nogais, and the results have been compared with these data for European, African, and East Asian ethnic groups. Daghestan is unique in its ethnic diversity, which is the greatest in the Caucasus: 26 out of approximately 50 autochthonous ethnic groups of the Caucasus live there. The genetic origin of this wide ethnic diversity of Daghestan and the Caucasus as a whole is still obscure. The genetic heterogeneity of Daghestan populations has been found to be lower than that of most other populations in the world. This is explained by a prolonged isolation and gene drift in their demographic history. Generalized genetic distances between ethnic groups calculated for the whole set of loci studied allow differentiating Asian populations from African ones, with European populations occupying intermediate positions. All Daghestan ethnic populations form a distinct common group together with some European populations (Finnish, Polish, and French). Nogais are genetically close to Southeast Asian populations. The genetic closeness and the apparently equal genetic diversity of Daghestan and European populations suggest that the ethnic differentiation of the ancestral populations of Daghestan and European ethnic groups occurred in the earliest populations of modern humans.