Purpose: Differentiated thyroid cancer (DTC) has variable degree of F-18 FDG avidity. The purpose of this study was to evaluate the relationship between F- 18 FDG uptake and pathological or immunohistochemical features of DTC. Materials and Methods: DTC patients who underwent both pre-operative F-18 FDG PET/CT scan and surgery were included in the study. Maximum standardized uptake values (SUVmax) of primary tumor were calculated. If the primary tumor showed no perceptibly increased F-18 FDG uptake, region of interest was drawn based on finding of CT portion of the PET/CT images. Pathological and immunohistochemical markers such as presence of lymph node (LN) metastasis and underlying thyroiditis, tumor size, Ki-67 labeling index, expressions of EGFR, COX-2, and Galectin-3 were evaluated. Results: Total of 106 patients was included (102 papillary carcinomas, 4 follicular carcinomas). The mean SUVmax of the large tumors (above 1 cm) was significantly higher than the mean SUVmax of small (equal to or less than 1 cm) ones (7.8¡¾8.5 vs. 3.6¡¾3.1, p=0.004). No significant difference in F-18 FDG uptake was found according to the presence or absence of LN metastasis and underlying thyroiditis, or the degree of Ki-67 labeling index, expression of EGFR, COX-2 and Galectin-3. Conclusion: In conclusion, the degree of F-18 FDG uptake in DTC was associated with the size of primary tumor. But there seem to be no relationship between F-18 FDG uptake of DTC and expression of Ki-67, EGFR, COX-2 and Galectin-3. (Nucl Med Mol Imaging 2009;43(1):40-47)