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Management of renal-cell carcinoma (RCC) in patients with Von Hippel–Lindau syndrome (VHL) represents a clinical dilemma: the oncologic outcomes must be weighed against preservation of renal function. Radiofrequency ablation (RFA) is currently used in selected cases for treatment of small-size RCC. The aim of this study was to evaluate the safety, complications, and functional and oncologic outcomes of RFA in the treatment of RCC in VHL patients.RCCs were treated with ultrasound-guided RFA or with laparoscopic RFA. Clinical and radiologic response, disease recurrence, and survival outcomes were evaluated during follow-up. Early and late complications were recorded and graded.Nine RCC patients underwent RFA. The median number of RCCs per patient was 3 (interquartile range, 2-4). Among these 9 patients, a total of 20 RCCs were treated by RFA (19 ultrasound-guided RFA and 1 laparoscopic procedure). Median RCC size was 2.5 cm (interquartile range, 2.0-3.0). RFA did not impair renal function (P = .35). In 2 cases disease persisted, and in 1 case disease recurred after 18 months. These patients were retreated with ultrasound-guided RFA with complete response and no renal function impairment. RFA treatment was overall well tolerated and safe. No complications were recorded. Postoperative stay was no longer than 1 day.RCC occurred in about two-thirds of VHL patients, who had young age at presentation; it was frequently multifocal and recurrent. The use of RFA, with extended indications, could represent a tailored treatment for VHL patients, reducing the risk of renal failure and resulting in satisfying oncologic results.Management of renal-cell carcinoma (RCC) in Von Hippel–Lindau syndrome (VHL) patients represents a clinical challenge. Radiofrequency ablation (RFA) is currently used in selected cases for treatment of small-size RCC. The aim of this study was to evaluate the safety and complication rate of RFA in treating RCC in VHL patients. The treatment did not impair renal function and resulted in complete oncologic control.