Phylogenetic relationships among 20 species-group taxa of Mustelidae, representing Mustelinae (Mustela, Martes, Gulo), Lutrinae (Enhydra), and Melinae (Meles), were examined using nucleotide sequences of the nuclear interphotoreceptor retinoid binding protein (IRBP) and mitochondrial cytochrome b genes. Neighbor-joining and maximum-parsimony phylogenetic analyses on these genes separately and combined were conducted. While IRBP performed better than cytochrome b in recovering more-inclusive clades, cytochrome b demonstrated more resolving power in recovering less-inclusive clades. Strong support was found for a close affinity of Enhydra with Mustela to the exclusion of Martes and Gulo (causing Mustelinae to be paraphyletic); the most-basal position of Mustela vison within Mustela, followed by Mustela erminea; an association of Mustela lutreola, Mustela itatsi, Mustela sibirica, and the subgenus Putorius (including Mustela putorius and Mustela eversmanii), to the exclusion of Mustela nivalis and Mustela altaica; and a basal position of Mustela itatsi to a clade containing Mustela sibirica and Putorius. Whereas cytochrome b strongly supported Mustela lutreola as the sister species to Putorius, IRBP strongly supported its basal placement to the Mustela itatsi-Mustela sibirica-Putorius clade. The low level of sequence divergence in cytochrome b between Mustela lutreola and Putorius is therefore a result of interspecific mitochondrial introgression between these taxa, rather than a recent origin of Mustela lutreola in a close relationship to Putorius. Time estimates inferred from IRBP and cytochrome b for mustelid divergence events are mostly in agreement with the fossil record.