NIS being the central molecule for DTC treatment, it is logical to study if its expression in the primary tumor would be helpful in predicting therapy response as well as tumor behavior and prognosis. Some studies tried to understand if NIS immunohistochemical expression in thyroid primary tumors would be helpful in predicting 131I uptake in recurrences and distant metastases. Although positive NIS immunostaining in primary tumors seemed to be predictive of positive recurrences and metastases on 131I scans, other studies did not distinguish whether NIS was expressed in the cell basolateral membrane, and negative NIS staining did not predict 131I scan-negative metastases (13, 15, 18). Even when only NIS membrane staining was considered, a negative NIS staining in the primary tumor was still not predictive of a negative 131scan of subsequent recurrences (29). To the best of our knowledge, there is only one study that addressed possible associations between NIS expression, evaluated by immunohistochemistry (IHC), and clinicopathological features and prognosis in a large series of thyroid primary tumors (1), reporting a significantly lower NIS expression in older patients (≥45 years) and also that NIS expression in the primary tumor was not useful as a prognostic marker.