Molecular phylogenies based on sequences of mitochondrial cytochrome b and nuclear IRBP genes are assessed on a comprehensive taxonomic sampling of African pygmy mice (subgenus Nannomys of the genus Mus). They represent a taxonomically diversified group of morphologically similar species, and exhibit an important chromosomal diversity, particularly involving sex-autosome translocations, one of the rarest and most deleterious chromosomal changes among mammals. The results show that the species sampled are genetically well differentiated, and that chromosomal rearrangements offer accurate diagnostic characters for discriminating most species. Furthermore, the species carrying different sex-autosome translocations appear monophyletic, suggesting that a genome modification allowing a higher rate of occurrence and/or fixation of such translocations took place, leading to the emergence of this lineage. In addition to taxonomic and biogeographical clarifications, we provide a temporal framework within which patterns of genic and chromosomal evolution are discussed.