PURPOSE: Troglitazone is a potent agonist for the peroxisome proliferator-activated receptor-gamma (PPARgamma), which is a ligand-activated transcription factor that regulates cell differentiation and growth. Antiproliferative effects of troglitazone have been reported in several human cancers including thyroid cancer. In the present study, we evaluated the redifferentiation effects of troglitazone in human cancers regarding the modulation of CD97 and sodium-iodide symporter (NIS) gene expression. METHODS: We used 3 human thyroid cancer cell lines: TPC-1 (papillary), FTC-133 (follicular), and XTC-1 (H rthle). Surface expression of CD97, a novel dedifferentiation marker, was measured by flow cytometry. mRNA expression of NIS gene was measured by real time quantitative PCR using TaqMan probe. RESULTS: Troglitazone down-regulated the surface expression of CD97 in FTC-133 cells and up-regulated (NIS) mRNA in TPC-1, FTC-133 and XTC-1 cells. CONCLUSION: Our investigations documented that troglitazone, a PPARgammaagonist, induced redifferentiation in thyroid cancer cell lines. In patients who have poorly differentiated thyroid cancer unresponsive to traditional treatments, PPARgammaagonists may therefore reintroduce the effectiveness of traditional treatments.