Previous authors have suggested that tumor suppressor expression promotes aging while preventing cancer, but direct experimental support for this cancer-aging hypothesis has been elusive. Here, by using somatic, tissue-specific inactivation of the p16^INK4a tumor suppressor in murine T- or B-lymphoid progenitors, we report that ablation of p16^INK4a can either rescue aging or promote cancer in a lineage-specific manner. Deletion of p16^INK4a in the T lineage ameliorated several aging phenotypes, including thymic involution, decreased production of naive T cells, reduction in homeostatic T-cell proliferation, and attenuation of antigen-specific immune responses. Increased T-cell neoplasia was not observed with somatic p16^INK4a inactivation in T cells. In contrast, B lineage–specific ablation of p16^INK4a was associated with a markedly increased incidence of systemic, high-grade B-cell neoplasms, which limited studies of the effects of somatic p16^INK4a ablation on B-cell aging. Together, these data show that expression of p16^INK4a can promote aging and prevent cancer in related lymphoid progeny of a common stem cell.