OBJECTIVE: To assess the relationship between long-term use of tamoxifen and endometrial cancer in patients with breast cancer. METHODS: A retrospective review of the 897 patients treated with tamoxifen after surgery at Asan Medical Center for primary breast cancer between January 1997 and December 2002 was done. All patients had received tamoxifen 20 mg/day for longer than 1 year. In this case-control study, there were 5 patients with endometrial cancer and 15 patients without endometrial cancer. Following variables including age, parity, body mass index, medical illnesses (e.g., diabetes, hypertension), family history of breast and gynecologic cancer, and duration of tamoxifen treatment were analyzed. RESULTS: The mean duration of tamoxifen treatment was 59 months in patients with endometrial cancer and 33 months in patients without endometrial cancer (p=0.003). There was no difference between two groups in other variables. CONCLUSION: It seems that long-term use of tamoxifen is associated with secondary endometrial cancer in primary breast cancer patients.