Aim of the study: To assess the role of FDG PET/CT in evaluation of differentiated thyroid cancer [DTC] patients with negative diagnostic radioactive I-131 scans [Dx-WBS] and elevated thyroglobulin compared to other PET and CT.Patients and methods: Forty patients with DTC and negative Dx-WBS underwent FDG PET/CT. Interpretation of side-by-side PET, CT and & fused PET/CT images was done. Data analysis for the patients and their lesions was done. The imaging findings were compared with histopathologic findings and/or their follow-up outcome. Results: One hundred eighty-one lesions found in the studied patients were evaluated. Diagnostic accuracy was 95% and 77.5% for FDG PET/CT and CT, respectively (P = 0.03). Regarding lesions analysis; accuracy and sensitivity of FDG fusion were significantly higher than CT in the detection of local recurrence, cervical nodal and distant metastases, except for pulmonary metastases. Integrated imaging added relevant information and changed patients’ management in 16 (44%) patients. Futile surgery was omitted in 3 patients where lung metastases were found.Conclusion: PET/CT has a significant role in detecting recurrence and distant metastases in DTC patients with elevated serum thyroglobulin and negative Dx-WBS. It improves diagnostic accuracy by providing precise functional and anatomical data better than CT or PET alone with optimal guidance for the management of such patients.