Serum thyroglobulin and imaging have been routinely used in the evaluation of thyroid cancer patients suspected of having metastatic or recurrent disease. A more sensitive technique capable of identifying the sites of disease not detected by current imaging methods might improve overall management. The objective in this study was to demonstrate the feasibility of using positron emission tomography (PET) for the detection of recurrent thyroid cancer. Thirty patients with a history of either papillary/follicular or medullary thyroid cancer suspected of having locally recurrent or metastatic cancer on the basis of elevated or rising blood markers were evaluated with PET. Imaging studies were performed with the radiotracer [F-18] fluorodeoxyglucose (FDG). A retrospective review of other imaging results was performed and compared to the PET results. PET was able to identify locally recurrent or metastatic papillary/follicular disease in all 24 patients studied with elevated or rising thyroglobulin. Similar results were obtained in 6 patients with medullary cancer recurrences in the presence of elevated calcitonin. In cases where follow-up data was obtainable (17/24 papillary/follicular cancers and 4/6 medullary cancers), disease was confirmed either directly by surgery and/or indirectly through changes or persistence of laboratory findings. The results support the hypothesis that in the presence of elevated blood markers indicative of recurrent thyroid cancer, PET may prove valuable as an adjunctive imaging test for identifying disease and influencing management in cases where conventional imaging fails to detect suspected disease.