Dedifferentiation of well-differentiated thyroid carcinoma is a well-known phenomenon that may lead to the disappearance of radioiodine uptake in tumors and the inability to treat patients with radioiodine. We report a patient in whom the 131I uptake progressively diminished to such low levels after a cumulative dose of 31.5 GBq that further 131I administration was considered nonbeneficial. Thereafter, metastases in the lungs and skeleton progressed. Because of the absence of any other therapeutic options, nearly 2 yr later we decided to reperform 131I measurements and scanning under hypothyroid conditions. All known metastatic lesions this time showed intense 131I uptake, more than 10-fold the previously measured values. High-dose 131I treatment was restarted.