The aim of this study was to evaluate the usefulness of 18-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) and technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) single photon emission computed tomography (SPECT) in detecting metastatic cervical lymph nodes (LN) in well-differentiated thyroid carcinoma (DTC) after total thyroidectomy and radioiodine-131 (I-131) treatments in patients with elevated serum human thyroglobulin (hTg) levels but negative I-131 whole body scan (WBS). Fifteen DTC patients underwent nearly total thyroidectomy and I-131 treatments with cervical LN metastases were included in this study. All subjects had negative I-131 WBS and elevated hTg levels (hTg > or = 10 microIU/ml) under thyroid-stimulating hormone (TSH) stimulation (TSH > or = 30 microIU/ml). FDG-PET could detect all of the 15 (100%) patients with metastatic cervical LN, but Tc-99m MIBI SPECT revealed lesions in only 9 out of 15 (60%) patients (p value < 0.05). This study demonstrated that FDG-PET is more sensitive than Tc-99m MIBI SPECT in detecting metastatic cervical LN in DTC with elevated serum hTg levels but negative I-131 WBS.