Introduction: In patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic procedures and in particular in spite of a negative iodine-131 scan. Positron emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful method for the detection of metastatic lesions or the recurrence of thyroid cancer. We aimed to investigate whether FDG-PET is capable of detecting metastastic lesions or recurrence in patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin, and otherwise negative diagnostic procedures, including the iodine-131 scan. Methods: From a group of 500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had elevated serum hTg-levels, negative iodine-131 scans, negative cervical and abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients (hTg 77.8+/-94.3 ng/ml. range 1.5-277 ng/ml, median 20 ng/ml), FDG-PET was per formed. All but one FDG-PET study was performed in a state of hypothyroidism (TSH 75.8+/-32.2 mu IU/ml, range 31 - 116 mu IU/ml, median 74.6 mu IU/ml). Results: In 6 of the 12 patients investigated, the FDG-PET was positive. In three of the patients, the diagnosis was confirmed by computed tomography or magnetic resonance imaging. In patients with a positive FDG-PET finding, the hTg level was 146.7+/-90.1 ng/ml (23-277 ng/ml, median 144.5 ng/ml). In contrast, in patients with a negative finding the hTg level was only 9.0+/-7.6 ng/ml (range 1.5-17 ng/ml, median 8.1 ng/ml), P=0.01. Conclusion: These preliminary results show that in patients with differentiated thyroid carcinoma, elevated hTg levels, and otherwise negative "conventional" diagnostic procedures, FDG-PET is helpful in detecting metastatic lesions.