Simple SummaryInherited renal cell carcinoma (RCC) typically presents earlier in life with multifocal and bilateral tumours. Treatment of such tumours is often challenging due to their bilateral presentation and high risk of recurrence or development of new disease. Therefore, the goal of treatment is to achieve oncological control while preserving renal function as much as possible. The purpose of this study was to evaluate the safety, efficacy, and preservation of renal function of percutaneous cryoablation (PCA) for small renal masses (SRM) in inherited RCC. We reviewed European data and found that image-guided cryoablation is safe, maintains good kidney function, and is effective in controlling cancer arising from hereditary small kidney cancers.AbstractThis study aims to evaluate the safety, efficacy, and renal function preservation of percutaneous cryoablation (PCA) for small renal masses (SRMs) in inherited RCC syndromes. Patients with inherited T1N0M0 RCCs (<7 cm) undergoing PCA from 2015 to 2021 were identified from the European Registry for Renal Cryoablation (EuRECA). The primary outcome was local recurrence-free survival (LRFS). The secondary outcomes included technical success, peri-operative outcomes, and other oncological outcomes estimated using the Kaplan–Meier method. Simple proportions, chi-squared tests, andt-tests were used to analyse the peri-operative outcomes. A total of 68 sessions of PCA were performed in 53 patients with RCC and 85 tumours were followed-up for a mean duration of 30.4 months (SD ± 22.0). The overall technical success rate was 99%. The major post-operative complication rate was 1.7%. In total, 7.4% (2/27) of patients had >25% reduction in renal function. All oncological events were observed in VHL patients. Estimated 5-year LRFS, metastasis-free survival, cancer-specific survival, and overall survival were 96.0% (95% CI 75–99%), 96.4% (95% CI 77–99%), 90.9% (95% CI 51–99%), and 90.9% (95% CI 51–99%), respectively. PCA of RCCs for patients with hereditary RCC SRMs appears to be safe, offers low complication rates, preserves renal function, and achieves good oncological outcomes.