OBJECTIVE.: Two polymorphisms affecting either expression (+331 G/A) or transcriptional activity (progins) of the progesterone receptor have been described. No clear correlation between either polymorphism and breast or ovarian cancer has been shown. Our objective is to clarify whether the two progesterone receptor polymorphisms modify the risk for breast or ovarian cancer. METHODS.: Healthy women and women suffering from either ovarian or breast cancer were enrolled in a case-control-based study to compare the frequencies of women carrying either one, both or none of the two polymorphisms. Patient and control populations resided in the same region of South Germany. PCR-RFLP analysis was used to determine the polymorphic alleles. RESULTS.: Women diagnosed with ovarian cancer showed a not significant increased frequency of +331 A carriers and a significantly increased frequency of progins carriers. Both polymorphisms appeared to be associated with a significantly increased risk for the disease in women below 51 years [OR: 4.1 (CI: 1.2-13.9) and 3.2 (CI: 1.1-9.1), respectively]. No association was detected between either of the two polymorphisms and breast cancer. Among ovarian and breast cancer patients, the number of individuals carrying both rare polymorphic alleles was significantly higher compared to healthy women. CONCLUSIONS.: Our findings support the hypothesis that low penetrant polymorphisms of progesterone receptor may modify the risk for ovarian cancer. Our data do not allow drawing a clear conclusion on the risk for breast cancer.