To determine whether PET could help differentiate malignant from benign thyroid tumors, 18F-fluorodeoxyglucose (FDG) accumulation and 201Tl scintigraphy were examined relative to histological diagnosis. METHODS Nodular thyroid lesions in 11 patients were evaluated before surgical resection. Static PET scanning with 370 MBq FDG was done for 20 min (from 40 to 60 min postinjection) in all patients, and standardized uptake values (SUVs) in these lesions were calculated. In addition, eight patients were evaluated with dynamic PET scan up to 60 min postinjection, and the lesions were further evaluated using graphical analysis. Thallium-201 delayed images were visually evaluated in 10 patients. RESULTS Four of 11 nodules were well-differentiated papillary carcinoma, another five were benign follicular adenomas, one was a multinodular goiter and another a case of chronic thyroiditis that was proved not to contain a nodule. Time-activity curves of FDG uptake showed different patterns in malignant and benign tumors. In the malignant tumors, FDG uptake increased with time after the tracer injection. By contrast, FDG uptake in benign tumors gradually decreased. With use of a cutoff value of 5.0 mg/ml for SUV and 10 microl x min(-1) x ml(-1) for Kc (K complex value determined using the linear fitting of the time-activity curve of FDG accumulation), all of the four malignant nodules and the six benign nodules were separated correctly. Chronic thyroiditis had high SUV in the malignant range. Of the four patients with thyroid carcinoma, the delayed 201Tl images revealed a slightly higher or equal uptake to background activity. In a patient with chronic thyroiditis, the delayed 201Tl images revealed diffuse accumulation higher than background activity. CONCLUSIONS FDG-PET is superior to 201Tl in differentiating malignant from benign tumors. Both SUVs and Kc values were useful indexes for this discrimination. Although careful evaluation is needed for chronic inflammatory lesions, this technique appears to be useful in evaluating thyroid nodules.