The standard treatment of differentiated thyroid cancer (DTC) consists of surgery followed by iodine-131 (¹³¹I) administration. Although the majority of DTC has a very good prognosis, more aggressive histologic subtypes convey a worse prognosis. Follow-up consists of periodically measurements of serum thyroglobulin, thyroglobulin antibodies and neck ultrasound and ¹²³I/¹³¹I whole-body scan. However, undifferentiated thyroid tumors have a lower avidity for radioiodine and the ability of DTC to concentrate ¹³¹I may be lost in metastatic disease. Positron emission tomography (PET)/computed tomography (CT) has been introduced in the evaluation of patients with thyroid tumors and the 2-[18F]-fluoro-2-deoxyd-glucose (¹⁸F-FDG) has been largely validated as marker of cell's metabolism. According to the 2015 American Thyroid Association guidelines, ¹⁸F-FDG PET/CT is recommended in the follow-up of high-risk patients with elevated serum thyroglobulin and negative ¹³¹I imaging, in the assessment of metastatic patients, for lesion detection and risk stratification and in predicting the response to therapy. It should be considered that well-differentiated iodine avid lesions could not concentrate ¹⁸F-FDG, and a reciprocal pattern of iodine and ¹⁸F-FDG uptake has been observed. Beyond ¹⁸F-FDG, other tracers are available for PET imaging of thyroid tumors, such as Iodine-124 (¹²⁴I), ¹⁸F-tetrafluoroborate and Gallium-68 prostate-specific membrane antigen. Moreover, the recent introduction of PET/MRI, offers now several opportunities in the field of patients with DTC. This review summarizes the evidences on the role of PET/CT in management of patients with DTC, focusing on potential applications and on elucidating some still debating points.