Microwave thermal ablation (MWTA) could be considered in the future for treating small solid renal masses. The aim of the present study was to determine both the tolerability of the new Amica-probe applicator-induced MWTA used in vivo on patients with solid renal masses and the effects of heating on renal tumors and normal renal parenchyma. Fourteen patients with renal masses eligible for open radical nephrectomy were enrolled in this phase I study. All patients underwent MWTA of renal masses during the open surgery procedure before clamping of renal vascular pedicle. The effects of MWTA on patients' coagulation and tumor/renal vasculature were investigated. The histological effects of MWTA on the tumor and intralesional vital tumor cell skipping were also evaluated. The MWTA-induced lesion diameters were measured to calculate both the overall ablation volume and the lesion sphericity index (SI). The Clavien-Dindo classification was used. In all patients the RENAL score was 9.4 (8-12) and the Charlson comorbidity index was 4.8 (3-7). MWTA-induced lesion size was 44.14 mm (±22.59). Mean SI was 1.08 (±0.2). No significant differences among coagulation clinical parameters were found. No local bleeding after MWTA treatment was reported. According to the Clavien-Dindo classification, there were two grade II perioperative complications due to the tumor extent but not related with the MWTA treatment. No residual vital tumor cells inside the MWTA-induced lesions were found. Telephone interview at 27.4 (±4.2) months mean follow-up did not find any long-term adverse events due to previous MWTA treatment. Amica-Probe applicator-induced MWTA is a safe and reproducible method to treat solid renal masses.