Patients with differentiated thyroid cancer generally have a good prognosis and high cure rates; however, subgroups of patients exist who develop progressive disease with significant morbidity and mortality. We analyzed the clinical outcome of patients with follicular thyroid cancer and distant metastases to define their presentation, impact of therapy and clinical outcome. A group of 44 patients with follicular thyroid cancer which had metastasized to the lungs or the skeleton was identified. All patients were treated at M.D. Anderson Cancer Center between 1965 and 1994. The group included 26 women and 18 men, with a median age of 56 years (range, 23 to 80 years). The primary tumor was limited to the thyroid in most cases. At the time of writing 13 patients were alive with metastatic disease a median of 43 months (range, 4 to 230 months) after diagnosis, while 27 patients died of thyroid cancer a median of 83 months (range, 4 to 238 months) after diagnosis. Bone pain was the chief complaint in almost all the 24 patients in whom distant metastases were present at diagnosis. In the 20 patients who initially presented with localized disease, distant metastases to the skeleton and/or lungs were detected after a median interval of 53 months (range, 8 to 216 months). Symptomatic spinal cord compression occurred in 13 patients and preceded their death by 4 to 34 months. Radioiodine uptake was seen in most bone metastases but in only about half of metastatic foci in the lungs. Radiotherapy was palliative and useful for bone metastases. We conclude that patients with follicular thyroid cancer and distant metastases have a distinct clinical profile that includes prominent skeletal and pulmonary involvement and substantial morbidity and mortality. Intensive multimodality therapy is required to optimize the clinical outcome.