Surprisingly, while moderate p53 increase is expected to decrease the tumor incidence as shown in Mdm2 hypomorphic mice (Mendrysa et al., 2006) and in Mdm2+/− or Mdm4+/− mice (Alt et al., 2003; Terzian et al., 2007), our Rps27l−/−;Trp53+/− mice have a much higher incidence than Rps27l+/+;Trp53+/− mice to develop spontaneous T-lymphoblastic and in rare case B-cell lymphomas, resulting in a shortened life-span. The gene discussed is TP53; the disease is B-cell non-Hodgkin lymphoma.