Mus lepidoides of central Burma (Myanmar) was described 75 years ago but has since been dismissed as a regional variant of the Indian field mouse, M. booduga. DNA sequences of multiple mitochondrial and nuclear genes from recently collected specimens, combined with a fresh morphological reassessment, reaffirm the distinctiveness of M. lepidoides from M. booduga and from all other species of Mus. Mus lepidoides is so distinct in fact that it warrants placement in its own Species Group within subgenus Mus. Molecular and morphological assessments of phylogenetic affinities converge on the exciting possibility that M. lepidoides represents the previously elusive sibling taxon to the Mus musculus Species Group. If confirmed, this relationship would provide the previously missing connection between the main radiation of subgenus Mus in Southeast and South Asia, and the radiation of the M. musculus Species Group in western Asia and Europe. We speculate that a common ancestor of M. lepidoides and the M. musculus Species Group occupied a continuous but episodic tract of xeric habitat that linked central Burma with northern India at various times during the late Pliocene and Quaternary. Further molecular and cytogenetic studies on the phylogenetic position of M. lepidoides clearly represent a high priority in mouse research.