To determine the incidence of clinically significant lesions in high-risk patients with atypical glandular cells (AGCs) after 4 to 6 years of follow-up, we reviewed repeated Papanicolaou (Pap) test and surgical pathology results for a 3-year period for 337 patients; 62 (18.4%) had only repeated Pap smears; 84 had Pap smear and histologic evaluations. In a range of repeated Pap smears from 1 to 11 (mean, 4.2), 9 patients had persistent AGCs/atypical squamous cells; remaining Pap smears were judged normal. Histologic follow-up revealed a clinically significant lesion in 110 (40.1%) of 274 patients--low-grade squamous intraepithelial lesion (LSIL), 46; high-grade squamous intraepithelial lesion (HSIL), 47; endocervical adenocarcinoma in situ (AIS), 3; endometrial hyperplasia, 4; endocervical or endometrial adenocarcinoma, 10. Among patients with histologic follow-up, 14 lesions (12.7% of patients with clinically significant lesions) were diagnosed after a mean of 37 months (range, 21-59 months): LSIL, 7; HSIL, 4; AIS, 1; endometrial adenocarcinoma, 2. Seven patients had negative cytologic and/or histologic evaluations between the initial cytologic AGC diagnosis and the final histologic diagnosis. Patients with AGCs are at risk of harboring clinically significant uterine lesions and should be followed up for a substantial period despite initial negative findings.