Since large trials have been set up to assess whether tamoxifen decreases the risk of breast cancer in healthy women, it has become important to investigate the drug's potential adverse effects, including occurrence of endometrial cancer. We undertook a case-control study in the Netherlands to assess the effect of tamoxifen on the risk of endometrial cancer after breast cancer. Through the population-based Netherlands Cancer Registry and two older, hospital-based, registries, we identified 98 patients who had endometrial cancer diagnosed at least 3 months after a diagnosis of primary breast cancer. Detailed information about treatment was obtained for all these patients, and for 285 controls, who were matched to the cases for age, year of breast cancer diagnosis, and survival time with intact uterus. Tamoxifen had been used by 24% of patients with subsequent endometrial cancer and 20% of controls (relative risk 1.3 [95% CI 0.7-2.4]). Women who had used tamoxifen for more than 2 years had a 2.3 (0.9-5.9) times greater risk of endometrial cancer than never users. There was a significant trend of increasing risk of endometrial cancer with duration of tamoxifen use (p = 0.049), and also with cumulative dose (p = 0.046). The duration-response trends were similar with daily doses of 40 mg or 30 mg and less. These findings support the hypothesis that tamoxifen use increases the risk of endometrial cancer. This oestrogenic effect on the endometrium was not related to the dose intensity. Physicians should be aware of the higher risk of endometrial cancer in tamoxifen users.