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OBJECTIVE To evaluate a new hybrid technique, which we defined as mini-laparoendoscopic single-site partial nephrectomy (MILESS-PN), for renal masses presenting an intermediate PADUA score. MATERIALS AND METHODS Forty consecutive cases of MILESS-PN performed between April 2013 and November 2015 were included in this study. Mini-laparoendoscopic single-site surgery consisted of the simultaneous use of two 3-mm pararectal trocars and an umbilical SILS trocar; the sequence of steps of MILESS-PN was comparable with standard laparoscopic partial nephrectomy. Demographic data and the main perioperative and oncological outcome parameters were gathered and analyzed. RESULTS The median operative time was 134.6 (interquartile range [IQR] 110-180) minutes with a median warm ischemia time of 12.1 (IQR 9.5-15.5) minutes. Postoperatively, 4 early complications were recorded and the median hospital stay was 4.2 (IQR 3.5-6.0) days. The median renal tumor size was 3.6 (IQR 2.4-5.3) cm with a median PADUA score of 8.3 (IQR 8-9). The definitive pathologic results revealed a renal cell carcinoma in 32 cases (80%), an angiomyolipoma in 3 cases (7.5%), and an oncocytoma in 5 cases (12.5%). All tumors were removed with negative surgical margins, and at the median follow-up of 34.5 (IQR 24-48) months, all patients were alive without evidence of tumor recurrence or port-site metastasis. A statistically significant decrease in the estimated glomerular filtration rate (eGFR) was observed postoperatively (postoperative vs preoperative median eGFR: 87.6 [IQR 70.4-101.8] and 104.7 [IQR 82.7-123.3], P <.0001) and at 6 months (6 months vs preoperative eGFR 93.6 [IQR 79.1-110.2] and 104.7 [IQR 82.7-123.3], P <.0001). CONCLUSION MILESS-PN for renal tumors with an intermediate PADUA score in well-selected patients is not associated with increased risks for the patients, presenting excellent oncological and functional results at the midterm follow-up. Mini-laparoendoscopic single-site surgery could represent a valid alternative to laparoendoscopic single-site surgery or minilaparoscopy because of its higher surgical reproducibility.