A small abut important subset of patients with differentiated thyroid cancer will die of disease. Our approach to therapy treats almost all patients similarly, with aggressive surgery and I-131 therapy. Meticulous follow-up should include multiple I-131 diagnostic scans using at least 5 to 10 mCi of I-131 with attention to proper patient preparation and good quality procedures. Thyroglobulin levels should be monitored, and other radiographic diagnostic procedures, including thallium scans and MR imaging, should be used as needed. Until screening tests are discovered which will accurately pinpoint patients at high risk for aggressive, recurrent thyroid cancer, the best course of action appears to be aggressive management, including radioiodine therapy.