While growth has been studied extensively in invertebrates, the mechanisms by which it is controlled in vertebrates, particularly in mammals, remain poorly understood. In this study, we investigate the cellular basis of differential limb growth in postnatal Monodelphis domestica, the gray short-tailed opossum, to gain insights into the mechanisms regulating mammalian growth. Opossums are an ideal model for the study of growth because they are born with relatively large, well-developed forelimbs and small hind limbs that must “catch up” to the forelimb before the animal reaches adulthood. Postnatal Days 1–17 were identified as a key period of growth for the hind limbs, during which they undergo accelerated development and nearly quadruple in length. Histology performed on fore- and hind limbs from this period indicates a higher rate of cellular differentiation in the long bones of the hind limbs. Immunohistochemical assays indicate that cellular proliferation is also occurring at a significantly greater rate in the long bones of the hind limb at 6 days after birth. Taken together, these results suggest that a faster rate of cellular proliferation and differentiation in the long bones of the hind limb relative to those of the forelimb generates a period of accelerated growth through which the adult limb phenotype of M. domestica is achieved. Assays for gene expression suggest that the molecular basis of this differential growth differs from that previously identified for differential pre-natal growth in opossum fore- and hind limbs. J. Exp. Zool. (Mol. Dev. Evol.) 322B: 221–229, 2014. © 2014 Wiley Periodicals, Inc.