Atypical glandular cells of undetermined significance (AGUS) is a diagnostic category of the Bethesda system encompassing glandular-type cells that show either endometrial or endocervical differentiation and display greater atypia than expected for a reactive process but do not meet the criteria for invasive adenocarcinoma. We investigated AGUS in a follow-up study of cervical-endocervical smears with either histology or repeat cytology follow-up. From the cytology files at Northwestern Memorial Hospital over a 4-year period, 136 cervical-endocervical smears were diagnosed with AGUS, which were further subdivided into atypical glandular cells, unqualified (AGC-U); atypical glandular cells, favor reactive (AGCFR); or atypical glandular cells, favor neoplasia (AGC-FN). Of 96 cases with either histologic or cytologic (cervical-endocervical smear) follow-up, 39 cases of AGC-U had a variety of diagnoses on follow-up, with mostly benign entities in 72% and squamous intraepithelial lesions in 28%. Follow-up of the 36 cases of AGC-FR also demonstrated mostly benign entities (82%) and five cases of squamous intraepithelial lesions. The largest number of premalignant and malignant diagnoses (48%) was found during follow-up of patients with an initial diagnosis of AGC-FN, including the only two cases of adenocarcinoma in situ in our study. In conclusion, our study confirms that AGUS encompasses a wide spectrum of diagnoses, most of which prove to be benign. Subclassification of these cases into “favor reactive” and “favor neoplasia” was found to be helpful in predicting the follow-up status of these patients. However, the small but distinctive percentage of preneoplastic and neoplastic diagnoses seen on follow-up warrant further diagnostic procedures and/or close monitoring in patients with this diagnosis.