Sodium iodide symporter is a transmembrane glycoprotein (codified by the SLC5A5 gene) expressed almost exclusively in the basolateral plasma membrane of thyroid follicular cells. It plays a central role in thyroid metabolism, mediating the active transport of iodine from the bloodstream into the follicular cells, the first step for thyroid hormones’ synthesis. NIS plays an essential role in the treatment of differentiated thyroid carcinomas (DTC), which usually maintain NIS expression, allowing the recognition and the treatment of recurrences and metastases with radioactive iodine (RAI) (1). Nonetheless, a significant subgroup of DTC patients with advanced disease lose NIS expression and become refractory to 131I; some of these patients die within 3–5 years (2). Furthermore, a study performed by Yildririm-Poyraz and coworkers (3) demonstrated that NIS expression in nontumoral thyroid tissues associates with higher rates of delayed structural response. NIS expression has been widely studied in normal thyroid and tumor tissues, on one hand to verify if its downregulation could be the molecular cause for the decrease of RAI uptake and on the other hand to understand the impairing mechanisms of NIS expression and function. However, no clear answer emerged from the results obtained in the previous studies. Despite the central role of NIS in diagnosis, treatment and follow-up of thyroid cancer patients, reliable methods for ascertaining NIS expression and functionality in clinical samples are not available.