We analyzed 47 cases of brain metastases from thyroid cancer seen at 1 institution over 5 decades. Brain metastases were a primary clinical feature at initial presentation in 15% of the cases, were identified during the subsequent course of the disease in 68%, and were only discovered at autopsy in 23%. The primary thyroid tumor was differentiated cancer in 68%, anaplastic cancer in 23%, and medullary cancer in 9%. Patients were typically older, with frequent evidence of aggressive disease and distant metastases at initial cancer diagnosis. Once brain metastases were diagnosed, disease-specific mortality was 78%, with a median product-limit survival of 4.7 months (67% and 12.4 months, respectively, for those with differentiated cancer). Resection of one or more foci of brain metastases significantly improved survival. The median disease-specific survival from diagnosis of brain metastases was 16.7 months for patients who underwent local excision of one or more brain metastases, compared with 3.4 months for those who did not (P < 0.05), independent of the presence of multifocal brain lesions. Recombinant human TSH safely stimulated radioiodine uptake for treatment of brain metastases in 1 patient. However, no evidence of survival benefit was found from radioiodine therapy, external beam radiotherapy, or chemotherapy. In summary, brain metastases fi om thyroid carcinoma are an extremely poor prognostic sign. Although selection bias and other unidentified factors inherent to retrospective analysis limit this conclusion, surgical resection of brain metastases may be associated with prolonged survival in differentiated carcinoma.