p21^Cip1 is a cyclin-dependent kinase inhibitor whose abundance increases in cells exposed to radiation or other DNA-damaging agents. Such increases activate a G1 checkpoint, which allows time for DNA repair before S phase entry. By inhibiting cell cycle progression, p21^Cip1 potentially suppresses tumorigenesis, and in support, we show that p21^Cip1 heterozygous and nullizygous mice develop more tumors than do wild-type mice when exposed to a single dose of γ-irradiation. Importantly, we also show that p21^Cip1 nullizygosity increases the incidence of metastatic tumors in irradiated mice. We suggest that p21^Cip1 is haploinsufficient for tumor suppression and functions as an antimetastatic agent.