In this report, the fourth of a revisionary series on mouse opossums (Marmosa), we treat the members of a monophyletic group of trans-Andean taxa that include M. alstoni (Allen, 1900); M. nicaraguae Thomas, 1905; and M. adleri, a new species. Although cytochrome b sequence divergence values among these species are substantially lower than distances commonly observed among other congeners, members of the Alstoni Group are strikingly unlike one another in morphological traits. We conjecture that rapid phenotypic divergence accompanied the Pleistocene radiation of an ancestral lineage that entered Central America as a late participant in the Great American Biotic Interchange. Additional undescribed species of the Alstoni Group seem likely to exist based on the evidence at hand, and we emphasize the need for renewed collecting in Central America, which has long been neglected by mammalian biodiversity researchers.