The objective of this study was to determine whether postmenopausal asymptomatic women with normal endometrial cells in their smear are at higher risk for endometrial pathology compared with women without these cells. Histologic follow-up outcome and otherwise cytologic follow-up of 29,144 asymptomatic postmenopausal women was determined. Presence of normal endometrial cells, age, use of hormones, and reported elevated maturation index were assessed. The effect of each variable on outcome as well as the combined effect were evaluated. Prevalence rate of (pre)malignant uterine disease was significantly higher when normal endometrial cells were found in the cervical smear (6.5%) as compared to smears without these cells (0.2%), resulting in a relative risk of 40.2 (95% CI 9.4–172.2). Neither age nor hormone use or elevated maturation index showed significant impact on the outcome. Asymptomatic postmenopausal women with normal endometrial cells in their smear are at significant higher risk for (pre)cancerous endometrial lesion than women without these cells. These cases should be reported to the physician with an explicit comment that normal endometrial cells in a smear of a postmenopausal woman is an abnormal finding, possibly associated with significant endometrial pathology. It raises the question whether further gynecological examination would be more appropriate.