The concentrations of endogenous hormones differ between women with twin and singleton births, with a possible influence on the risk of cancer. We used the nationwide Swedish Family-Cancer Database, including 30,409 women with a twin birth, to examine the subsequent risks of breast, endometrial, and ovarian cancers. Relative risks (RRs) were calculated in a log-linear Poisson regression model of person-years as offset. Cancer data were retrieved from the Swedish Cancer Registry; a total of 1010, 210, and 174 women were diagnosed with breast, endometrial, and ovarian cancers respectively, after a twin birth. A significant decrease in the risk of breast cancer was noted among women with a twin birth compared with women with a singleton birth (RR 0.85, 95% confidence interval (CI) 0.74-0.98). The protective effects were observed throughout the intervals after last pregnancy and they were strongest shortly after the last pregnancy in women who delivered a twin birth before 30 years of age. Twin birth did not change the risk of endometrial cancer (1.08, 95% CI 0.79-1.47) but the RR was increased for women with the number of pregnancies > or =4 (1.39, 95% CI 1.11-1.76). The RR for ovarian cancer was 0.95 (95% CI 0.79-1.15). Our study showed that twin births significantly reduced the subsequent risk of breast cancer. However, the associations of twin births with endometrial and ovarian cancers were not substantial.