In the present review we discuss the indications and clinical results of positron emission tomography (PET) in patients affected by differentiated thyroid cancer. It is well known that in this type of tumor the most used scintigraphy is based on 131-Iodine or 123-Iodine administration. However, a fraction of these tumors looses its capability to trap radioactive Iodine (this usually happens after multiple 131-Iodine treatments). This Iodine-negative- tumors are more frequently observed in the elderly and are characterized by a higher aggressiveness. Due to the poor clinical results of external radiotherapy and chemotherapy surgery remains the treatment of choice. Surgery can be performed with curative purposes also if the metastatic spread is visualized in an early phase. Among the various scintigraphic and radiologic techniques used, PET and PET-CT are reaching an even more important role in the early diagnosis of small tumoral deposits of thyroid cancer. The other issue we discuss in the present review is the potential value of PET and PET-CT in the differential diagnosis of suspected thyroid nodules.