Since the specific accumulation of iodide in thyroid was found in 1915, radioiodine has been widely applied to diagnose and treat thyroid cancer. Iodide uptake occurs across the membrane of the thyroid follicular cells and cancer cells through an active transporter process mediated by the sodium iodide symporter (NIS). The NIS coding genes were cloned and identified from rat and human in 1996. Evaluation of the NIS gene and protein expression is critical in the management of thyroid cancer, and several approaches have been tried to increase NIS levels. Identification of the NIS gene has provided a means of expanding its role in the radionuclide gene therapy of nonthyroidal cancers as well as thyroid cancer. In this article, we explain the relationship between NIS expression and the treatment of thyroid carcinoma with I-131, and we include a review of the results of our experimental and clinical trials.