The 2001 Bethesda System revision recommends reporting benign-appearing endometrial cells (BAEMC) in all women 40 years or older, not just in postmenopausal women. We studied the influence of this change on clinical practice and the detection of endometrial neoplasia. Women 40 years or older were selected for study if BAEMC were reported on a cervical cytologic specimen. Cases were stratified by implementation of the 2001 guidelines. Results of endometrial biopsies within 18 months, with special attention to the frequency of adenocarcinoma and hyperplasia, were assessed. In the preimplementation group, BAEMC were reported as an epithelial cell abnormality in 154 postmenopausal women and as an incidental finding in 636 premenopausal women (total = 790). In the postimplementation group, BAEMC were reported in 836 women. The proportion of endometrial biopsies in these cohorts was significantly increased (P < .05). After implementation of the 2001 guidelines, the detection of endometrial cancer increased (6 vs 3 cases, not significant). Of the women with cancer, 3 were premenopausal, 5 were asymptomatic, and 2 were premenopausal and asymptomatic. All cancers were identified in women older than 45 years, suggesting that the Bethesda cutoff of 40 years is safe and conservative.