The immune response can effectively hamper the progression of preclinical stages of tumor growth. Medicine in the postgenomic era offers an increasing possibility of detecting healthy individuals at risk of developing cancer who could benefit from tumor-preventive vaccines. The identification of novel tumor antigens that fulfill two conditions will be crucial for the development of cancer immunoprevention. First, an ideal antigen should have a crucial pathogenetic role in tumor growth to avoid the selection of antigen-loss variants. Second, the antigen should be recognizable by the immune system even in MHC-loss variants and should therefore be recognized both by antibodies and T cells. Identifying such antigens will also provide new targets for cancer immunotherapy.