To evaluate the role of chest computed tomography (CT) in patients with head and neck squamous cell carcinoma (HNSCC) and to determine the optimal timing and predictive factors for positive findings. Design: Retrospective analysis. Setting: Tertiary referral center. Patients: Two hundred seventy screening chest CT scans performed in 192 patients with HNSCC during a 42month period were reviewed. Main Outcome Measures: The scans were categorized as new cases, follow-up cases, or recurrent cases. The results were classified as abnormal or normal. Scans of patients having a radiologic diagnosis of a malignant neoplasm of the lung or an indeterminate lesion were considered abnormal. Factors correlating with an abnormal chest CT scan or development of malignant neoplasm of the lung were analyzed, including the timing of imaging and the patients' clinicopathologic data. Results: Seventy-nine scans (29.3%) were considered abnormal. The rate of an abnormal scan was significantly higher in the follow-up case group (44.2%) than in the new case group (14.2%) (P Ͻ.001). Ten of 15 indeterminate scans (66.7%) with small (Ͻ1 cm) solitary pulmonary nodules showed disease progression on subsequent follow-up scans, changing the patients' diagnoses to a malignant neoplasm of the lung. The predictive factors for development of a malignant neoplasm of the lung were initial N2 or N3 disease, stage IV disease, recurrent disease, and distant metastasis to another site. Conclusions: Chest CT is recommended for high-risk patients, especially during the follow-up period. Intensified evaluation and management are mandatory for indeterminate small solitary pulmonary nodules because of the high rate of malignant neoplasms.