Abstract: As the thyroidal membrane protein that mediates iodide transport into thyroid follicular cells, NIS plays a key role in thyroid pathophysiology and allows very effective use of radioiodine for therapy of thyroid cancer. Most studies have demonstrated decreased NIS expression levels in thyroid carcinomas. Retinoic acide and demethylation as well as histone deacetylase inhibitors treatment, have been explored with the aim of stimulating NIS expression and optimizing therapeutic responsiveness to ¹³¹I in thyroid cancer. In addition, cloning and molecular analysis of the NIS gene offer the possibility of a novel cytoreductive gene therapy strategy based on targeted NIS gene transfer into thyroidal tumors.