Two cases of endometrial sarcoma that developed many years after exposure to unopposed exogenous and endogenous estrogens, with no previous pelvic irradiation, are described. The literature is reviewed and the possible effect of prolonged unopposed estrogen stimulation is suggested as an etiologic factor in such extremely rare conditions. These cases add additional support to the assumption that prolonged and excessive endogenous or exogenous unopposed estrogen stimulation of the uterus may increase the risk of endometrial sarcoma.