We previously identified cyclin B1-specific T cells and antibodies in cancer patients with cyclin B1-positive (+) tumors and also in some healthy individuals. We also demonstrated that these responses may be important in cancer immunosurveillance by showing that vaccination against cyclin B1 prevents growth of transplantable cyclin B1(+) tumors in mice. Constitutive overexpression of cyclin B1 was determined to correlate with the lack of p53 function. This allowed us to use p53(-/-) mice as a model that better approximates human disease. These p53(-/-) mice spontaneously develop cyclin B1(+) tumors. At 5-6 weeks of age, when the mice were still healthy with no evidence of tumor, they received the cyclin B1 vaccine and were then observed for tumor growth. We demonstrate that cyclin B1 vaccination delays spontaneous cyclin B1(+) tumor growth and increases median survival of tumor-bearing p53(-/-) mice.