OBJECTIVE The incidence of synchronous primary endometrial and ovarian cancer is 2- to 10-fold higher than that expected based on the incidence of each cancer alone. We sought to evaluate reasons for this in a case-control study. METHODS We combined data on a maternal history of cancer and reproductive and menstrual factors from 56 women with synchronous multiple primary disease who had participated in three population-based studies of gynecologic cancer. For comparison, we analyzed the same information from 280 women with endometrial cancer alone, 280 with ovarian cancer alone, and 280 without a history of either cancer. RESULTS The reduced risk of multiple primary disease associated with high parity (2 or more births vs 0: OR = 0.37, 95% Cl, 0.19-76) and long-term use of oral contraceptives (12 or more months vs none: OR = 0.60, 95% Cl, 0.24-1.5) tended to be more pronounced than that associated with endometrial cancer alone or with ovarian cancer alone. CONCLUSIONS Though limited by relatively small numbers, our results suggest that the presence of some common etiologies is a basis for the unusually high co-occurrence of endometrial and ovarian cancers.