Bcl11b+/- heterozygous mice and Bcl11b+/-p53+/- doubly heterozygous mice showed more susceptibility to gamma-ray-induced thymic lymphomas than Bcl11b wild-type mice and p53+/- mice, respectively. Most of the thymic lymphomas developed in irradiated Bcl11b+/-p53+/- mice retained the Bcl11b wild-type allele, indicating that Bcl11b is a haploinsufficient tumor suppressor gene. Of interest is the high retention of the wild-type Bcl11b allele in those radiation-induced tumors, and this leads to the implication that the main contribution of irradiation in the Bcl11b+/-p53+/- mice is not to tumor initiation, by inducing allelic losses, but to the promotion of thymic lymphoma development. Although the reason for this unexpected high retention is unclear, an explanation might be the apoptosis given by loss of Bcl11b in the Jurkat T-cell line, because apoptosis appears to contradict the predicted property of tumor suppressors. Our chapter also shows the presence of clonally growing large thymocytes in atrophic thymuses at 40 days after irradiation. Those cells are probably prelymphoma cells because of the genetic alteration detected. However, the cell number was low, and therefore abrogation of the hindrance in cell proliferation through additional genetic and/or epigenetic changes may be a prerequisite for lymphoma development.