OBJECTIVES: To investigate the utility of positron-emission tomography-computed tomography (PET-CT) in identifying distant metastatic disease in patients with previously untreated head and neck squamous cell cancer (HNSCC) prior to definitive treatment. MATERIALS AND METHODS: Retrospective analysis of 27 consecutive patients with previously untreated HNSCC who underwent PET-CT imaging in addition to chest radiography (CXR) as part of their metastatic workup. RESULTS: The majority of patients (89%) had TNM stage III or IV disease. PET-CT was suspicious for pulmonary malignancy in four (15%) patients and indeterminate in one (4%) patient. CXR was suspicious for pulmonary malignancy in two (7%) patients. Pulmonary metastases or a new lung primary was present in 3 (11%) patients: 3 of 4 (75%) patients with positive PET-CT scans and 0 of 23 (0%) patients with negative or indeterminate PET-CT scans compared with 2 of 2 (100%) patients with positive CXR and 1 of 25 (4%) patients with negative CXR. The sensitivity and specificity of PET-CT in predicting pulmonary malignancy was 100% and 96%, respectively, with a positive predictive value of 75% and a negative predictive value of 100%. The sensitivity and specificity of CXR in predicting pulmonary malignancy was 67% and 100%, respectively, with a positive predictive value of 100% and a negative predictive value of 96%. Including nonpulmonary sites, the overall incidence of distant metastatic disease was 19% (5/27) with 11% (3/27) unsuspected prior to PET-CT. CONCLUSIONS: PET-CT improves detection of metastatic disease in the high-risk patient and should be performed as part of the routine pretreatment evaluation of patients with advanced stage HNSCC.