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The objective of this study is to investigate the effect of menstrual and reproductive variables, breastfeeding, exogenous hormones, and gynecological conditions on endometrial cancer risk. We conducted a case-control study in Italy, including 454 women with endometrial cancer and 908 hospital controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression models. Endometrial cancer risk was inversely associated with age at menarche (OR = 0.7, 95% CI = 0.5-1.0, for > or =14 vs. <12 years), and directly associated with age at menopause (OR = 1.8, 95% CI = 1.1-2.7, for > or =55 vs. <50 years) and years of menstruation (OR = 2.4, 95% CI = 1.7-3.4, for highest vs. lowest tertile). Multiparity strongly reduced the risk among women under 60 years of age (OR = 0.3, 95% CI = 0.2-0.6, for > or =3 deliveries vs. <2). Oral contraceptive use conferred a 40% reduced risk (95% CI = 0.4-1.0), irrespective of time since cessation. Although based on small numbers, women with a history of treated infertility (OR = 2.7, 95% CI = 1.1-6.4) or endometriosis (OR = 4.0, 95% CI = 1.0-15.5) were at increased risks. No significant associations with endometrial cancer risk emerged for age at first/last birth, breastfeeding, menopausal status, hormone replacement therapy, and history of uterine fibromyomas or polycystic ovary. In conclusion, this study confirms the importance of multiparity, years of menstruation, and oral contraceptive use in endometrial cancer etiology, thus contributing to identify women at elevated risk of such neoplasm.