We analyzed data from a population-based case-control study of endometrial cancer. Our goal was to identify a subgroup of women in whom the additional cancer risk associated with unopposed estrogen use was sufficiently small so as to not be a deterrent to taking a hormone preparation of this type. Researchers interviewed women with endometrial cancer (N = 553) and controls (N = 752) regarding hormone use. The additional risk of endometrial cancer associated with unopposed estrogen use did not vary substantially in the presence or absence of hypertension, parity, oral contraceptive use, or smoking. The results suggest that, although heavier women may experience a greater risk of endometrial cancer associated with unopposed estrogen use (8.2 per 1,000 per year) than lighter women (4.2 per 1,000 per year), long-term users in the latter group nonetheless face a substantial absolute increase in risk. We conclude that subdividing women on the basis of the presence or absence of other known risk factors for endometrial cancer fails to delineate a subgroup that is exempt from the increased risk of this cancer associated with use of unopposed estrogens. 83.6% of estrogen users reported taking conjugated estrogens.