This paper reports macro‐ and microscopic changes in hyperfunctioning thyroid nodules (HTN), initially diagnosed as solitary, in patients treated with percutaneous ethanol injection (PEI). In 78 patients, benign solitary HTN were diagnosed by clinical and hormonal examination. High resolution ultrasonography confirmed the solitary nodule. The results of fine needle aspiration biopsy (FNAB), performed twice, ruled out malignancy of the nodule. The patients were referred for PEI treatment. At 1‐year follow‐up, newly formed thyroid nodules, whose volumes increased, were detected in five patients (6.4%) with HTN, initially diagnosed as solitary. Therefore, these patients were operated on. Subtotal thyroidectomy was performed. At the intraoperative macroscopic evaluation, a hard fibrous solid mass was found in place of three nodules (n1, n2, n3) following PEI treatment. The middle area of the cut surface of PEI‐treated nodules (n4 and n5) in the other two patients was firm and haemorrhagic, surrounded by a fibrous mass. Histolopathologic examination of n1, n2 and n3 revealed fibrosis and hyalinosis. Examination of n4 and n5 showed haemorrhagic necrosis in the middle of the nodules surrounded by fibrous tissue.