Benign thyroid cysts often recur after aspiration; the effectiveness of tetracycline instillation in the case of recurrence has been questioned. We, therefore, tested the efficacy of percutaneous ethanol injection in 20 patients with "pure" cyst relapsing after aspiration. After evacuation, 95% ethanol was instilled under sonographic guidance and re-aspirated 5 min later. The procedure was performed twice for larger cysts. Follow-up studies were carried out after 1, 3, 6, and 12 months. In case of recurrence at 1 month, patients (n = 5) were submitted to a second session. A slight burning sensation was the only adverse effect. No recurrences were observed at 3 and 6 month follow-up; only one patient with recurrence after 1 month had relapsed at 12 months. A significant shrinkage (P < 0.0001 vs. pretreatment) was observed in all other cases at 12 months; cysts were not detectable in seven patients (35%). No significant variations in thyroid hormone levels were detected during treatment or follow-up. Serum thyroglobulin levels markedly increased 3 h after ethanol injection. One month after treatment, thyroglobulin returned to pretreatment levels, thus excluding progressive thyroid damage. Percutaneous ethanol injection may prove a safe and effective tool for the therapy of thyroid cysts.