Tamoxifen is widely used nowadays in the management of breast cancer, having established its efficacy in this indication, especially for postmenopausal patients with ER-positive breast tumours. However, tamoxifen has recently been recognized as carcinogenic for the human endometrium, probably with an effect of duration of treatment. Moreover, this drug may be associated with the occurrence of endometrial cancers of unusual histological types and/or of a more aggressive nature. We describe a case series of 11 patients who developed such cancers after having previously received tamoxifen for breast cancer. Several assumptions on the mechanisms underlying the attributed carcinogenic properties of tamoxifen, for the endometrium and potentially for other organs, are discussed on the basis of current knowledge.