This prospective study was performed to evaluate the ability of a dual-head gamma camera with fluorine-18 fluorodeoxyglucose coincidence detection emission tomography (FDG-CDET) to detect primary tumor and cervical lymph nodes in head and neck squamous cell carcinoma (HNSCC), and to show the response of the carcinoma to chemotherapy. The findings were compared with those of physical examination, computed tomography (CT), and histopathology, before treatment in 61 patients, and after induction chemotherapy in 34 of them. Before treatment, the primary was detected in 93%, 79%, and 95% of cases on panendoscopy, CT, and FDG-CDET, respectively. After chemotherapy, 34 patients were evaluable for response of the primary tumor. Surgical resection was performed in 23 of them: agreement with histopathologic results for response to treatment was 74%, 69%, and 78% for panendoscopy, CT, and FDG-CDET, respectively. No surgical resection was performed in 11 of the 34 patients, but biopsies were performed before radiotherapy, and their rates of agreement with histopathologic results for response to treatment were 75%, 75%, and 67% on panendoscopy, CT, and FDG-CDET, respectively. For cervical lymph nodes, 245 sites were resected in 41 patients, and FDG-CDET appeared competitive with CT in detecting metastatic neck disease, especially after neoadjuvant chemotherapy; the accuracy was 93%. These results demonstrated the ability of FDG-CDET to detect primary tumors and cervical lymph nodes in HNSCC and to show its response to chemotherapy, as compared to the ability of CT and panendoscopy. It may be a complementary tool to evaluate residual disease after induction chemotherapy, although higher sensitivity would be required for FDG-CDET to be considered as a staging modality.