Percutaneous laser ablation (PLA) is a new method to be used for reducing the volume of symptomatic cold benign thyroid nodules. We aimed to introduce the long-term histopathological effects of PLA procedure in thyroid nodules. A 42-year-old male patient with 18.7-mL nodule volume was transferred a total of 720 J of energy with 3-W power. A 50-year-old female patient with 14.1-mL volume nodule was transferred a total of 3,300 J with 5-W power. A 61-year-old female patient with 49.7-mL volume nodule was transferred a total of 4,200 J with 5-W power. The thyroidectomy materials were examined histopathologically 2 years later. In histopathologic examination, it was observed that the periphery of ablated area was organized with hyalinized connective tissue and the center was organized with necrosis and carbon particles. Concurrently, in the center, we detected calcifications and colloid and foreign-body giant cells against colloid in one patient. We did not encounter any pathologic findings in the tissue adjacent to ablated area. In the cold benign thyroid nodules taken out by thyroidectomy 2 years after PLA procedure, necrosis and hyalinization were detected histopathologically. PLA procedure in cold benign thyroid nodules seems to be safe according to long-term histopathological findings. © Humana Press Inc. 2009.