In summary, the absence of BRAF and NRAS mutations in every carcinoma displaying NIS membrane staining at immunohistochemistry supports the assumption that the genetic background of tumors may be of major importance to SLC5A5 expression as well as to NIS targeting to the basolateral membrane. On the other hand, NIS immunohistochemical expression did not predict tumor behavior, therapy response or outcome. Moreover, SLC5A5 mRNA expression was significantly lower in mutated PTCs and a lower SLC5A5 mRNA expression was associated with tumor aggressiveness and worse prognosis. Thus, the study of SLC5A5 mRNA expression is much more informative compared to NIS expression evaluated by IHC.