OBJECTIVE: To prospectively evaluate the use of 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) in the initial staging of squamous cell head and neck carcinoma. SUMMARY BACKGROUND DATA: The status of cervical lymph nodes is an important prognostic factor and determinant of management approach in squamous cell head and neck cancer. METHODS: FDG-PET findings were compared with those of computed tomography (CT) before removal of the primary tumor and/or neck dissection. Histopathologic analysis was used as the gold standard for assessment of the sensitivity and specificity of these modalities. RESULTS: FDG-PET correctly identified the primary tumor in 35 of 40 patients in whom the site of the primary was known clinically and still present (sensitivity 88%). None of four unknown primaries were detected. Tumors not detected by FDG-PET were generally superficial, with depths of less than 4 mm. CT correctly identified 18 of the 35 primary tumors (sensitivity 51%). Eleven of 17 CT false-negative tumors were detected by FDG-PET. The sensitivity and specificity for the presence of metastatic neck disease on FDG-PET were 82% and 100%, respectively; those for CT were 81% and 81%, respectively. FDG-PET was true positive for metastatic neck disease in two of the three CT false-negative patients. CONCLUSIONS: FDG-PET shows promise in the initial staging of head and neck cancer and provides additional accuracy to a conventional staging process using CT.