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To assess the long-term efficacy of radiofrequency ablation (RFA) and percutaneous ethanol (EtOH) injection treatment of local recurrence or focal distant metastases of well-differentiated thyroid cancer (WTC).RFA and EtOH injection techniques are new minimally invasive surgical alternatives for treatment of recurrent WTC. We report our experience and long-term follow-up results using RFA or EtOH ablation in treating local recurrence and distant focal metastases from WTC.Twenty patients underwent treatment of biopsy-proven recurrent WTC in the neck. Sixteen of these patients had lesions treated by ultrasound-guided RFA (mean size, 17.0 mm; range, 8–40 mm), while 6 had ultrasound-guided EtOH injection treatment (mean size, 11.4 mm; range, 6–15 mm). Four patients underwent RFA treatment of focal distant metastases from WTC. Three of these patients had CT-guided RFA of bone metastases (mean size, 40.0 mm; range, 30–60 mm), and 1 patient underwent RFA for a solitary lung metastasis (size, 27 mm). Patients were then followed with routine ultrasound, 131I whole body scan, and/or serum thyroglobulin levels for recurrence at the treatment site.No recurrent disease was detected at the treatment site in 14 of the 16 patients treated with RFA and in all 6 patients treated with EtOH injection at a mean follow-up of 40.7 and 18.7 months, respectively. Two of the 3 patients treated for bone metastases are free of disease at the treatment site at 44 and 53 months of follow-up, respectively. The patient who underwent RFA for a solitary lung metastasis is free of disease at the treatment site at 10 months of follow-up. No complications were experienced in the group treated by EtOH injection, while 1 minor skin burn and 1 permanent vocal cord paralysis occurred in the RFA treatment group.RFA and EtOH ablation show promise as alternatives to surgical treatment of recurrent WTC in patients with difficult reoperations. Further long-term follow-up studies are necessary to determine the precise role these therapies should play in the treatment of recurrent WTC.