Tamoxifen is a selective oestrogen receptor modulator (SERM) with anti-oestrogenic properties in the breast and oestrogenic effects in tissues such as bone and the cardiovascular system. It is an excellent breast cancer drug for all stages of the disease. Its SERM profile makes it a valuable alternative to hormone replacement therapy, especially for women at high risk of breast cancer. Tamoxifen, however, increases the incidence of benign and malignant lesions of the uterus. Secondary prevention of these, early detection and treatment, is feasible but not cost-effective in breast cancer patients because potential endometrial risks do not outweigh beneficial effects in the breast. This may be different in healthy women with an as yet unknown benefit on breast cancer mortality. We review the literature on the importance of tamoxifen's endometrial lesions and balance available evidence on whether and how best to screen them. In a subset of tamoxifen users it seems advisable to assess the uterine cavity prior to intake with a yearly endometrial assessment as pointed out, starting 3 years after initiation of treatment. In most cases there is endometrial thickening on ultrasonographic assessment and additional tests such as hydrosonography or hysteroscopy are required to confirm an empty atrophic uterus as remains the case in most asymptomatic women on tamoxifen. Newer compounds, such as raloxifene, have a similar SERM profile to tamoxifen but are neutral on the uterus. This has recently been proven by 3 years of endometrial follow-up data. Longer endometrial safety will hopefully confirm these early findings. Whether other SERMs in development are better, and which of them is better for the breast, is to be demonstrated in ongoing studies.