18Fluorine-fluorodeoxyglucose (FDG) positron-emission tomography (PET) has emerged as a useful method in various fields of oncology. The aim of the present study was to evaluate the clinical significance of this technique in differentiated thyroid carcinoma and to compare the results with other imaging modalities, particularly with whole-body 131iodine scintigraphy (WBS) and hexakis (2-methoxyisobutylisonitrile) (99m)technetium (I) scintigraphy (MIBI). Whole-body PET imaging using FDG was performed in 54 patients. There were 39 patients with papillary tumors and 15 patients with follicular tumors (including 3 Hürthle-cell carcinomas). Primary tumor stage (pT) was pT1 in 5 cases, pT2 in 19 cases, pT3 in 2 cases, pT4 in 24 cases, and unknown in 4 cases, respectively. Finally, for each case an overall clinical evaluation was done including histology, cytology, thyroglobulin level, sonography, computed tomography, magnetic resonance imaging, and subsequent clinical course, to allow a comparison with functional imaging results. Compared with WBS, FDG-PET gave different results in the majority of cases with recurrence/metastases (11 FDG-true-positive/WBS-negative tumor sites and 8 WBS-true-positive/FDG-negative tumor sites). In 7 patients with recurrence/metastases, FDG-PET and WBS gave corresponding results (10 sites). In 28 patients, FDG-PET and WBS were normal (including 2 false-negative cases). MIBI was performed in 44 cases. FDG-PET was better correlated to MIBI (congruent positive results in 13 tumor sites) than to WBS. Compared with MIBI, FDG-PET was superior in 5 cases (including 3 patients with distant metastases). Two FDG-negative/MIBI-positive tumors were observed. Different tracer uptake mechanisms have to be considered regarding "nonspecific" tumor imaging with FDG-PET or MIBI. Nevertheless, since spatial resolution with respect to tomographic imaging is inferior with single photon emission computer tomography (SPECT) using MIBI, the observed higher sensitivity of PET might be due to the higher spatial resolution of this method. As far as grading could be obtained, FDG-PET seemed to be more sensitive than WBS in high-grade tumors, whereas WBS was positive predominantly in low-grade carcinomas, although statistical significance could not be reached. The results prove the clinical usefulness of FDG-PET and MIBI for detection of 131iodine-negative tumor tissue in differentiated thyroid cancer.