The usefulness of combined 2-[18F] fluoro-2-deoxy-D: -glucose positron emission tomography and computed tomography (FDG-PET/CT) in locating suspected recurrence in patients with iodine-negative differentiated thyroid cancer (DTC) was evaluated. Thirty-six patients with DTC and suspected iodine-negative recurrence underwent restaging with FDG-PET/CT. The images of CT, FDG-PET, both modalities viewed side by side (CT+PET), and FDG-PET/CT were evaluated by two physicians separately. Imaging results were correlated with either histology (n = 20) and/or clinical follow-up of at least 36 months. Recurrent disease was diagnosed in 22/36 patients. FDG-PET alone, CT alone, CT+PET, and FDG-PET/CT showed a sensitivity of 82%, 73%, 91%, and 96%, respectively. Specificities were 79%, 71%, 79%, and 100%, respectively. FDG-PET/CT significantly improved specificity compared with CT+PET and resulted in a further treatment modification in 5/36 patients (14%). CT alone was especially sensitive for lung metastases, FDG-PET alone for the remainder of the body. Accurate fusion of functional and morphologic data by FDG-PET/CT improves the staging accuracy of patients with suspected recurrence of iodine-negative DTC. This has an impact on patient management in a substantial number of patients.