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Objectives Data on Papanicolaou (Pap) tests with atypical glandular cells (AGCs) with concurrent squamous cell abnormalities (AGC + Sq) are limited. We evaluated histologic outcomes and the role of high-risk human papillomavirus (HR-HPV) testing in this setting compared with AGCs without concurrent squamous cell abnormalities (AGC-alone). Methods This study used a retrospective cohort of patients with Pap test diagnoses of AGC + Sq and AGC-alone between October 2013 and August 2021. Results We included 287 Pap tests from 278 patients. The HR-HPV test was positive in 55% of AGC + Sq cases and 14% of AGC-alone cases (P < .0001). Most AGC + Sq cases displayed squamous lesions (41.5%) or were benign (41.5%) on histology, whereas AGC-alone cases were predominantly benign (72%) or extracervical neoplasms (18%). AGC + Sq cases showed higher rates of significant histologic lesions (P = .0001), which were associated with positive HR-HPV status (P = .0012). In AGC-alone cases, HR-HPV status was associated with significant histology only in patients 50 years of age or younger. In both groups, 20% or more of HR-HPV–negative patients harbored significant lesions. Conclusions AGC + Sq represents a distinct group of patients. HR-HPV testing and patient age provide useful information in the evaluation of AGC, but triage based on HR-HPV testing is not recommended because of the potential for missing significant lesions.