The sodium iodide symporter (NIS) is an intrinsic plasma membrane protein mediating the active transport of iodide in the thyroid gland and a number of extrathyroidal tissues, in particular in the lactating mammary gland. Because of its crucial role for the ability of thyroid follicular cells to trap iodide, cloning of NIS opened up an exciting and extensive new field of thyroid-related research. Cloning and molecular characterisation of NIS allows investigation of its expression and regulation in thyroidal and non-thyroidal tissues and its potential pathophysiological and therapeutic implications in benign and malignant thyroid disease. In addition to its key function in thyroid physiology, NIS-mediated iodide accumulation allows both diagnostic thyroid scintigraphy and the effective therapeutic application of radioiodine in benign and malignant thyroid disease. Characterisation and application of NIS as a novel therapeutic gene for cytoreductive gene therapy of extra-thyroidal tumours and the presence of high endogenous NIS expression in the majority of breast cancers further suggest a promising role of NIS in the diagnosis and treatment of cancer outside the thyroid gland.