Second malignant neoplasms were evaluated among 32,251 women with ovarian cancer, including 4,402 10-year survivors, within the nine population-based registries of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute (1973–1992) and the Connecticut Tumor Registry (1935–1972). Overall, 1,296 second cancers occurred against 1,014 expected [observed/expected (O/E), 1.28; 95% confidence interval (CI), 1.21–1.35]. Sites contributing 25 or more excess cancers included leukemia (O/E, 4.17; O, 111; 95% CI, 3.43–5.03) and malignancies of colon (O/E, 1.33; O, 188; 95% CI, 1.15–1.54), rectum (O/E, 1.43; O, 76; 95% CI, 1.13–1.79), breast (O/E, 1.18; O, 404; 95%, CI 1.07–1.30), and bladder (O/E, 2.07; O, 65; 95% CI, 1.59–2.63). Ocular melanoma (O/E, 4.45; O, 8; 95% CI, 1.92–8.77) was also significantly increased. Second cancer risk was high during all follow-up intervals, and cumulative risk at 20 years was 18.2%, compared with a population expected risk of 11.5%. Statistically significant relationships existed between serous adenocarcinoma of the ovary and breast cancer (O/E, 1.29; 95% CI, 1.06–1.56) and mucinous ovarian adenocarcinoma and rectal cancer (O/E, 1.95; 95% CI, 1.09–3.22). Secondary leukemia appeared linked with antecedent chemotherapy, whereas radiotherapy was associated with cancers of connective tissue, bladder, and possibly pancreas. Genetic and reproductive factors predisposing to ovarian cancer may have contributed to the elevated risk of breast and colorectal neoplasms and possibly ocular melanoma. Thus, excess malignancies following ovarian cancer represent complications of curative therapies and/or underlying susceptibility states that have etiological and clinical ramifications.