To evaluate safety and diagnostic yield of percutaneous CT-guided biopsy of extrarenal upper urinary tract lesions. Retrospective review of our institutional database of image-guided biopsies yielded 44 CT-guided percutaneous biopsies in 44 unique patients that targeted ureteral (30, 68%) or other non-renal upper urinary tract lesions (14, 32%) between January 1, 2000 and May 1, 2017. Indications, pre-biopsy imaging, biopsy technique, peri-procedural antithrombotic use, complications including bleeding defined by Society of Interventional Radiology criteria, pathology results, and subsequent imaging were reviewed up to 3 months after the procedure to evaluate safety and diagnostic yield. Mean patient age was 66 (range 27-88) and 23/44 patients were male. The majority (34/44) of lesions were sampled with an 18-gauge biopsy device via a 17-gauge introducer needle, and the remaining 10/44 lesions were sampled with a 19/20 gauge system. The mean number of core samples obtained was 4 (range 2-10). No major complications occurred. Specifically, no patient developed a urine leak or urinary obstruction. Minor complications occurred in 3/44 (7%) biopsies, all retroperitoneal hemorrhages that did not require transfusion or other intervention. Biopsy was adequate for pathologic examination in 41 of 44 (93%) cases. Among patients undergoing surgical resection, biopsy diagnosis was concordant with surgical pathology in 9/10 (90%) cases and discordant in 1/10 (10%). CT-guided percutaneous biopsy of upper urinary tract lesions can be performed safely, with high diagnostic yield, and with a high rate of concordance on subsequent surgical pathology.