Radioactive iodine-refractory thyroid cancer (TC) has a poor prognosis, and restoring iodine uptake is a major therapeutic goal. Recent studies have used tyrosine kinase inhibitors (TKIs) for 3-6 wk to achieve redifferentiation, but preclinical data suggest that maximal effects occur within 8-12 d. In this retrospective study, 8 patients with metastatic radioactive iodine-refractory TC received trametinib plus dabrafenib (for -mutated disease) or trametinib alone (for wild-type disease) for 10 d. Iodine uptake was assessed by I-scintigraphy; responders received high-dose radioactive iodine therapy, and nonresponders continued TKIs for another 10 d. Two patients (both with wild-type disease) achieved successful iodine uptake restoration with significant thyroglobulin reduction after radioactive iodine therapy. Extending TKI treatment to 21 d did not yield further benefit. Our pilot study supports preclinical findings that maximal restoration of iodine uptake is achieved after only 10 d of TKI therapy, reducing toxicity and treatment costs. Longer treatment did not provide any additional benefit. Larger prospective trials are needed to confirm these findings.