To ascertain the significance of squamous atypia encountered during routine Papanicolaou smear screening in an older population, we reviewed 115 consecutive patients over age 50 seen during a 3-year period. Evaluation included repeating the smear and performing colposcopy in all patients. Colposcopically directed biopsy and endocervical curettage were performed when appropriate. Sixty-seven patients (58.3%) had atrophy, 43 (37.4%) were normal, two (1.7%) had cervical intraepithelial neoplasia grade 1, two (1.7%) had cervical intraepithelial neoplasia grade 2, and one (0.9%) had human papillomavirus (HPV) infection. There was a strong association between squamous atypia and estrogen deficiency. With the correction of the estrogen deficiency, the squamous atypia reverted to normal in a statistically significant percentage of patients. A Papanicolaou smear report of squamous atypia in women over age 50 should not be considered normal; further evaluation is required. The incidence of cervical or vaginal intraepithelial neoplasia and HPV infection is much lower than reported in studies involving younger patients.