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Background: To evaluate the diagnostic accuracy of (18)F-FDG PET/CT in detection of recurrent differentiated thyroid cancer (DTC) in patients with elevated stimulated thyroglobulin (Tg) or anti-Tg antibody (Ab) levels, and negative (131)I whole body scan according to the Tg level. Methods: PET/CT images of well DTC patients who had total thyroidectomy and radioiodine ablation were included. Patients showing elevated Tg titer (≥2.0 ng/ml after TSH stimulation) or elevated anti-Tg titer (≥70.0 IU/ml) while diagnostic radioiodine scan was negative were enrolled. PET/CT was classified as positive or negative on the basis of visual interpretation. The maximum standard uptake values (SUVmax) of the suspected lesions on PET/CT were also recorded. The PET/CT findings were compared with histological or clinical follow-up results based on other imaging modalities and serum Tg/anti-Tg Ab titers. The diagnostic performance of PET/CT was compared among 4 subgroups according to the Tg level [2 ng/ml ≤ stimulated Tg (sTg) < 5 ng/ml, 5 ng/ml ≤ sTg < 10 ng/ml, 10 ng/ml ≤ sTg < 20 ng/ml, and ≥20 ng/ml]. Results: A total of 68 PET/CT images from 60 patients were included, and histological confirmations were available in 32 images. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of PET/CT were 69.4, 66.7, 69.1, 95.6, and 17.4%, respectively. There were 3 PET/CT cases with high anti-Tg Ab level, and low (<2 ng/ml) Tg level, and all 3 were positive of recurrence. The mean SUVmax of the suspected lesions on PET/CT was 2.9 ± 4.5 (range 1.3-29.7). The sensitivity of PET/CT according to Tg levels was 28.6% when Tg was between 2 and 5, 57.1% between 5 and 10, 60.0% between 10 and 20, and 85.7% when Tg was equal to or greater than 20 ng/ml sub-groups, respectively. Conclusion: Diagnostic accuracy of FDG PET in radioiodine negative thyroid cancer may vary depending on serum Tg levels at imaging. (18)F-FDG PET/CT is useful in detection and localization of recurrent thyroid cancer in patients with negative diagnostic radioiodine scan despite elevated Tg greater than 20 ng/ml or high anti-Tg Ab titers. In contrast, PET/CT provides little additional information when the Tg is less than 5 ng/ml. [ABSTRACT FROM AUTHOR]