INTRODUCTION: In case of pelvic recurrence of colorectal cancer, reirradiation of previously irradiated patients may increase the rate of salvage radical resection. Due to the high cumulative dose, one of the main concerns is radiation-induced lumbosacral plexopathy. This report describes multiple irradiations of a lesion adjacent to the lumbosacral plexus, using a highly selective technique, which allows optimal sparing of such a critical structure. Case description A 53-year-old woman treated in 2008 for a locally advanced rectal adenocarcinoma with preoperative pelvic irradiation and concomitant chemotherapy followed by surgery had disease recurrence in 2011 and underwent a second course of pelvic radiotherapy. In December 2015, magnetic resonance imaging showed a single local recurrence infiltrating the muscle next to the right lumbosacral plexus and close to the cauda equina. Repeat reirradiation was planned. The total dose deriving from the previous treatment plans was assessed by nonrigid image registration using the dedicated tool implemented in MIM 6.1.7 (MIMvista Corp., Cleveland, OH). The treatment was performed with Cyberknife (Accuray, Sunnyvale, CA) with a schedule of 20 Gy in 5 fractions (4 Gy per fraction). The dose was prescribed to 70% isodose and target coverage was 97%. Two months after the treatment, magnetic resonance imaging showed a decreased signal and stable disease with no change in tumor size. Conclusions This case report suggests that pelvic re-reirradiation might be a possibility in very carefully selected cases of rectal cancer, using high-precision radiation modalities.