Small mammals are rarely reported from subfossil sites in Madagascar despite their importance for paleoenvironmental reconstruction, especially as it relates to recent ecological changes on the island. We describe the uniquely rich subfossil small mammal fauna from Ankilitelo Cave, southwestern Madagascar. The Ankilitelo fauna is dated to the late Holocene (∼500 years ago), documenting the youngest appearances of the extinct giant lemur taxa Palaeopropithecus, Megaladapis, and Archaeolemur, in association with abundant remains of small vertebrates, including bats, tenrecs, carnivorans, rodents, and primates. The Ankilitelo fauna is composed of 34 mammalian species, making it one of the most diverse Holocene assemblages in Madagascar. The fauna comprises the 1st report of the short-tailed shrew tenrec (Microgale brevicaudata) and the ring-tailed mongoose (Galidia elegans) in southwestern Madagascar. Further, Ankilitelo documents the presence of southwestern species that are rare or that have greatly restricted ranges today, such as Nasolo's shrew tenrec (M. nasoloi), Grandidier's mongoose (Galidictis grandidieri), the narrow-striped mongoose (Mungotictis decemlineata), and the giant jumping rat (Hypogeomys antimena). A simple cause for the unusual small mammal occurrences at Ankilitelo is not obvious. Synergistic interactions between climate change, recent fragmentation and human-initiated degradation of forested habitats, and community-level processes, such as predation, most likely explain the disjunct distributions of the small mammals documented at Ankilitelo.