BACKGROUND AND METHOD: As genetic alterations in the gene for the peroxisome proliferator-activated receptor gamma (PPARgamma) have been described and PPAR agonists have been shown to redifferentiate thyroid cancers in animal models, we performed a pilot study in five patients with thyroglobulin-positive and I scan-negative thyroid cancers using the PPARgamma agonist rosiglitazone. RESULTS: Although thyroglobulin levels increased in four of the five patients after 3 months of treatment with rosiglitazone, the I scan remained negative in four patients and became only faintly positive in one patient for two lung metastases that could be correlated with metabolically active lung metastases shown by F-fluorodeoxyglucose positron emission tomography (F-FDG PET) and by computed tomography (CT). F-FDG PET, performed in four patients, revealed metastases of significant size in two patients, including the patient mentioned above and in a second patient confirmed by surgery. CONCLUSIONS: Treatment with rosiglitazone increased the production of thyroglobulin in some patients with thyroid cancers, but only rarely restored scintigraphically significant iodine trapping. It remains to be shown whether longer treatment periods might result in a more efficient redifferentiating effect.