Abstract Background By combining trocar sites and extraction incision, Laparo-endoscopic Single-site Surgery (LESS) may provide less morbidity than traditional laparoscopy. Concerns continue about LESS for locally advanced tumors. We present our experience with LESS-radical nephrectomy with renal vein thrombectomy (LESS-RN-RVT) Case Presentation Between 5-6/2009, 2 patients underwent LESS-RN-RVT (1 right-/1 left-side). Standard steps of multi-site laparoscopic radical nephrectomy were performed, including stapled renal vein thrombectomy and intact specimen extraction. Both cases were successfully completed by LESS without complications. Mean tumor size was 7.8 cm, incision size 4.5 cm, operative time 152 min, EBL 100 ml, and hospital stay 2.5 days. Both patients had negative margins, and are alive at time of last follow-up. One did not require postoperative opiates. Conclusions LESS-RN-RVT is safe and feasible in selected patients with renal vein thrombi. Further accumulation of data and comparison to multiport laparoscopic technique are requisite.