The sodium iodide symporter (NIS) is a plasma membrane protein that is responsible for iodide transport into thyroid cells. To understand the regulation and expression of human NIS (hNIS) in papillary thyroid carcinomas, we evaluated the expression levels of hNIS mRNA in primary and lymph node metastatic papillary carcinoma tissues. The correlation of mRNA levels between hNIS and thyroid-specific genes, thyrotropin (TSH) receptor, and thyroglobulin (Tg), were also investigated. Twenty-three cases of papillary carcinoma and 7 pairs of primary and lymph node metastastic tissues were included in this study. We measured the expression levels of hNIS, TSH receptor, and Tg mRNAs by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay (RPA). The levels of hNIS mRNA in lymph node metastatic tissues were evaluated by RT-PCR. By semiquantitative RT-PCR, 87% of papillary carcinoma (20/23) expressed hNIS mRNA, but the degrees of expression were variable and were lower than those of normal thyroid tissues. The decreased expression of hNIS mRNA in papillary carcinoma compared to normal thyroid tissue was also noticed by RPA. All 23 papillary carcinomas in this study showed the expression of TSH receptor and Tg mRNAs. The levels of TSH receptor mRNA were again lower in papillary thyroid carcinomas than in normal controls. The level of hNIS mRNA was correlated with the levels of TSH receptor (r = 0.449, p < 0.05), but not with Tg mRNA. In addition, significant correlation of mRNA level was observed between TSH receptor and Tg (r = 0.706, p < 0.01). Two of six lymph node metastatic tissues did not show hNIS mRNA even with significant hNIS expressions in papillary carcinoma tissues in thyroid. The levels of hNIS expression of the remaining four lymph node metastatic tissues were lower than those of corresponding primary tissues. Interestingly, one case showed no hNIS expression in primary tissue, but significant hNIS expression in lymph node metastatic tissue. No correlation was found in hNIS mRNA expression between primary and lymph node metastatic tissues. Our results suggest that the measurements of hNIS mRNA level in primary tissues may not predict the therapeutic response to radioactive iodine.