Tamoxifen, a nonsteroidal antiestrogen, was first approved by the Food and Drug Administration in 1978 for the treatment of patients with breast cancer. Large clinical trials involving over 75,000 patients have demonstrated an improved recurrence-free and overall survival benefit in both premenopausal and postmenopausal women. Long-term adjuvant tamoxifen is the endocrine treatment of choice for selected patients with breast cancer, and there are currently large-scale trials to evaluate its role as a chemopreventative agent in healthy women at risk for breast cancer. Consequently, a large number of women, including healthy young patients with no history of cancer, will be subjected to the long-term effects of tamoxifen. One of the most significant complications of long-term tamoxifen use is the possible development of endometrial cancer. The purpose of this chapter is to review the current literature regarding tamoxifen use in breast cancer patients and associated benign and malignant uterine neoplasia. In addition, the role of screening for endometrial cancer in tamoxifen-treated breast cancer patients is explored.