BACKGROUND: An association between melanoma and endometriosis has been reported, but most findings relied on case-control studies or a limited number of melanoma cases, and therefore the available evidence is weak. Moreover, the effect of other benign gynecological diseases on melanoma risk is unknown. METHODS: We prospectively studied data from the Etude Epid?ologique aupr?de femmes de la Mutuelle G?rale de l'Education Nationale cohort, which includes 98 995 French women, insured by a national health scheme mostly covering teachers, aged 40 to 65 years at inclusion. Data on history of endometriosis and other benign gynecological diseases were regularly collected, starting in 1990. Relative risks and 95% confidence intervals were computed using Cox proportional hazards regression models. RESULTS: During 12 years of follow-up, 363 melanoma cases were ascertained among 91 965 subjects. A history of endometriosis (n = 5949) was significantly associated with a higher risk of melanoma (relative risk, 1.62; 95% confidence interval, 1.15-2.29). There was also a significantly increased risk among women with a history of fibroma (n = 24 375), compared with those who had no such history (relative risk, 1.33; 95% confidence interval, 1.06-1.67). A history of ovarian cyst, uterine polyp, breast adenoma/fibroadenoma, or breast fibrocystic disease was not significantly associated with risk. CONCLUSIONS: These data provide the strongest evidence to date of a positive association between a history of endometriosis and melanoma risk. The association between fibroma and melanoma, which has not been previously described, warrants further investigation.