Objective: To determine the prevalence of cervical intraepithelial neoplasia (CIN) in women who are infected with human immunodeficiency virus (HIV) and who have mild cytologic atypia. Methods: As part of an ongoing, prospective study of cervical disease in HIV-infected women, Papanicolaou smears were analyzed cross-sectionally for the diagnosis of mild cytologic atypia. Results: Mild cytologic atypia was diagnosed in 112 (25%) of the 453 HIV-infected women enrolled in this study, compared with 36 (9%) of the 401 HIV-uninfected women (odds ratio [OR] 3.3, 95% confidence interval [CI] 2.2-5.1; P < .001). Mild cytologic atypia was diagnosed more frequently in HIV-infected women with lower CD4+ T-lymphocyte counts (χ2 for trend, P = .015) and in those with a history of an abnormal Papanicolaou smear or treatment for cervical disease (OR 3.0, 95% CI 1.2-7.6; P = .008). Coexistent CIN was detected by colposcopically directed biopsy in 42 (38%) of the 112 HIV-infected women with mild cytologic atypia, compared with five (14%) of the 36 HIV-uninfected women (OR 3.7, 95% CI 1.3-11.9; P=.008). Severe inflammation with associated epithelial reparative atypia was diagnosed in 90 (20%) of the HIV-infected women and in 87 (22%) of the HIV-uninfected women. Coexistent CIN was detected in 12% of the HIV-infected women with severe inflammation and associated epithelial reparative atypia, compared with 2% of the HIV-uninfected women with this cytologic diagnosis (OR 5.9, 95% CI 1.2-23; P=.01). Conclusion: Mild cytologic atypia, a frequent diagnosis on Papanicolaou smears from HIV-infected women, is associated with CIN. We recommend that all HIV-infected women with mild cytologic atypia be referred for colposcopy.