A 45-year-old female patient with autosomal dominant polycystic kidney disease (ADPKD) and a horseshoe kidney underwent right laparoscopic nephrectomy. The indication for nephrectomy was to create space within the right iliac fossa for renal transplantation. The operation proceeded as routine for laparoscopic nephrectomy for ADPKD, but was uniquely challenging due to the large size and extensive vasculature of the polycystic horseshoe kidney. In addition to documenting the feasibility of the pure laparoscopic approach for nephrectomy in patients with ADPKD and horseshoe kidney, this case highlights the abnormal location and vasculature encountered when operating on horseshoe kidneys.