Nine patients with suspicious thyroid nodules were studied with positron emission tomography (PET) following the administration of [18F]-2-deoxy-2-fluoro-D-glucose (FDG) prior to surgical excision. Three patients were ultimately determined to have papillary carcinoma, four were shown to have follicular adenomas, and two were proven to have multinodular goiters with dominant nodules. All three malignancies and four of the six benign lesions were easily detected visually as areas of increased FDG uptake. While visual analysis alone did not discriminate between the benign and malignant lesions, all three malignancies had dose uptake ratios (DURs) for FDG in excess of 8.5 while the DURs for benign lesions ranged between 1.9 and 6.3. The mean FDG DUR for the three papillary carcinomas (10.9 +/- 3.9; mean +/- SD) was significantly greater (p = 0.0019) than that of the six benign lesions (3.2 +/- 1.7). There was no significant difference between the FDG DUR for the follicular adenomas and the dominant nodules of multinodular goiters. Further research is needed to confirm the usefulness of PET in the differential diagnosis of thyroid nodules, and, in particular, whether or not PET can discriminate between benign and malignant follicular neoplasms.