We performed a retrospective study of 47 patients to ascertain the ability of combined positron-emission tomography and computed tomography (PET/CT) to localize recurrent head and neck cancer. When clinically warranted, biopsies were performed in an attempt to obtain pathologic confirmation of the PET/CT findings. Of the 47 patients, 33 exhibited PET/CT findings consistent with recurrent cancer. Of the 33 patients, 25 underwent either biopsy or surgical excision of disease in an attempt to obtain a pathologic confirmation. Biopsy analysis confirmed the PET/CT findings in 22 of these patients; in the remaining 3 patients, pathologic findings were inconsistent with the PET/CT diagnosis. Based on the subset of 25 patients who underwent pathologic testing, the sensitivity of combined PET/CT was 95% and the specificity was 60%. We conclude that combined PET/CT imaging is a valuable tool for localizing tumor recurrence in patients with head and neck cancer.