Sp100 is a single-copy gene in the human and the mouse. A related gene, Sp100-rs, occurs in multiple copies and forms a conspicuous cluster in the mouse chromosome 1. Murine Sp100 and Sp100-rs are homologous from the promoter up to a position in intron 3, but they differ 3' of that position. In the genus Mus, Sp100-rs is present in one phylogenetic branch, represented by the house mouse, M. musculus, but probably does not exist in another branch, represented by M. caroli. Thus, Sp100-rs arose relatively late in the evolution of the genus Mus, whereas Sp100 existed in the common ancestor of the human and the mouse. The Sp100-rs gene cluster probably evolved by gene fusion followed by amplification and diversification.