The purpose of this study was to compare optimized whole-body (WB) and dedicated high-resolution contrast-enhanced PET/CT protocols and contrast enhanced CT in the preoperative staging of primary squamous cell carcinoma of the head and neck. Methods: A total of 44 patients with clinically M0 squamous cell carcinoma of the head and neck underwent primary tumor resection and neck dissection within 6 wk of diagnostic imaging. Imaging consisted of a standard WB PET/CT protocol without intravenous contrast enhancement, followed by a high-resolution dedicated head and neck (HN) PET/CT protocol, which included diagnostic-quality contrast-enhanced CT (CECT). Imaging results were compared with histopathology. A 5-point scale was used to designate primary tumor localization and the presence of lymph node metastasis on a per-patient and per-level basis. For cervical nodes, receiver-operating-characteristic curves were generated to determine the differences in performance between the WB and HN PET/CT protocols and CECT. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for primary tumor and cervical nodes. Results: No statistical difference was observed between WB and HN PET/CT protocols, both of which significantly outperformed CECT, in the evaluation of the primary tumor. The performance of the HN PET/CT protocol was superior to that of the WB PET/CT in the detection of cervical node metastases, achieving statistical significance on a per-level basis and approaching significance on a per-patient basis, with the greatest advantage in the detection of small positive lymph nodes (,15 mm). No significant difference was observed between the WB PET/CT protocol and CECT in nodal staging, either on a per-patient or on a per-level basis. Conclusion: The primary advantage of the dedicated HN PET/CT protocol over the WB protocol or CECT in the staging of head and neck cancer is in the detection of small lymph node metastases.