The key role of p53 as a tumor suppressor became clear when it was realized that this gene is mutated in 50% of human sporadic cancers and germline mutations expose to cancer along lifespan. Mutations in this gene not only abolish the tumor suppressive functions of p53 but also equip the protein with new pro-oncogenic functions. Here, we review the mechanisms by which these new functions gained by p53 mutants promote tumorigenesis.