Pencil-tailed Tree Mice (Muridae: Chiropodomys) are small arboreal mammals endemic to the rainforests of Southeast Asia. They are capable of manual and pedal grasping and have nails rather than claws on their pollex and hallux, but their limb morphology has never been analyzed from functional, ecogeographic, or taxonomic perspectives. We compared two species of Chiropodomys to the similarly sized but terrestrial Mus musculus using quantitative morphometric osteological data recorded from six limb bones. Principal components analysis (PCA) clearly separated Chiropodomys from Mus. Multivariate and univariate analyses revealed several features linked to arboreality in Chiropodomys and characteristics associated with terrestriality in Mus. These include a wide medial epicondyle and shallow knee in Chiropodomys and a long olecranon process, long greater trochanter, and deep knee in Mus. PCA also distinguished mainland C. gliroides from island C. calamianensis of the Palawan Faunal Region, with the latter exhibiting larger body size, as predicted by the island rule. Finally, PCA clearly separated northeastern C. gliroides specimens collected north of the Isthmus of Kra from southwestern specimens collected on the Malay Peninsula south of the Isthmus of Kra; these preliminary results may indicate that there are two distinct taxa in this sample, but this must be tested with more specimens and data. Overall, our study revealed functional differences related to substrate preference, larger body size in an island endemic species, and postcranial evidence for an additional mainland taxon.