Lymphoma is the third most common cancer diagnosed in children and T cell lymphoma has the worst prognosis by clinical observation. So far, a lymphoma model with uniform penetrance has not been available. In this paper, we generated a p53 deficient mouse model by targeting embryo stem cells derived from the C57BL/6 mouse strain. Homozygous p53 deficient mice exhibited more accelerated rate of spontaneous tumorigenesis with a high spontaneous occurrence rate (93.3%) of malignant lymphoma. Because tumour models with a high phenotypic consistency are currently needed, we further generated the lymphoma model by single intraperitoneal injection of 37.5 or 75 mg/kg N-methyl-N-nitrosourea (MNU) to p53 deficient mice. Lymphoma and retinal degeneration occurred in 100% of p53 +/mice administrated higher concentration of MNU, which was much higher than previously reported models. The main anatomic sites of lymphoma were thymus, spleen, bone marrow, and lymph nodes. Both induced and spontaneous lymphomas in the thymus and spleen were stained positive for CD3 antigen. Furthermore, positive CD4 and/or positive CD8 cells were detected by flow cytometry, indicating a T-cell lineage of the lymphomas. The onset time of this uniform lymphoma model was from 13 to 17 weeks after the administration of MNU accompanied by the second time of weight loss. Based on our observations and previous data, we hypothesised that mice with the B6 background are prone to lymphomagenesis. This model could be used to study the mechanisms of lymphomagenesis, to select new drugs, and to improve the reproducibility of experimental results.