In this study, we analyzed p53 alterations and their impact on prognosis in ovarian cancer. We performed analyses of the p53 mutational status and its protein expression of 107 ovarian cancer patients. Moreover, the single nucleotide polymorphism SNP309 in the P2-promotor of the MDM2 gene was investigated. A large group of patients with p53 overexpression despite having a wild-type gene were identified. This was associated with a significantly shortened overall survival time. Patients with p53 alterations were also more refractory to chemotherapy than patients with normal p53. The G-allele of the SNP309 is associated with an earlier age of onset in estrogen receptor expressing FIGO stage III patients. In contrast, in FIGO III patients, a weakened p53 pathway, either G-allele of SNP309 or a p53 mutation, is correlated with an increased overall survival compared with patients whose tumors are wild-type for p53 and SNP309.