The inadequacies of athymic mice for research with grafted tumors are well known. Monodelphis domestica, the laboratory opossum, has the potential to complement the rodent model because of the immunoincompetent window period during early marsupial development. We injected pups of different ages with mouse melanoma cells and human melanoma, colon, and prostate cancer cells. The results showed that the xenogeneic tumors can grow and metastasize. We also obtained positive results by heterotopically injecting juveniles with mouse melanoma cells. These results establish Monodelphis as a natural mammalian model to study the cascade of interactions between xenografted cells and the host system.