Schwannomas of the colon and rectum are uncommon and incompletely characterized tumors, and only a small number of cases have been reported. This study was undertaken to determine the clinicopathologic profile of such tumors. A total of 20 colorectal schwannomas were identified and analyzed in a review of 600 mesenchymal tumors of the colon and rectum from the files of the Armed Forces Institute of Pathology. The schwannomas occurred equally in men (n = 9) and women (n = 11) in a wide age range (18-87 years; median age 65 years). The most common location was cecum (n = 7), followed by sigmoid and rectosigmoid (n = 6), transverse colon (n = 3), descending colon (n = 2), and rectum (n = 1); the location of one tumor had not been specified. The tumors commonly presented as polypoid intraluminal lesions, often with mucosal ulceration. Rectal bleeding, colonic obstruction, and abdominal pain were the most common presenting symptoms. The most common histologic variant (n = 15) was a spindle cell schwannoma with a trabecular pattern and vague or no Verocay bodies. These tumors ranged from 0.5 to 5.5 cm in diameter. A lymphoid cuff with germinal centers typically surrounded these tumors and focal nuclear atypia was often present, but mitotic activity never exceeded 5 per 50 HPF. All four epithelioid schwannomas occurred in the descending colon or sigmoid, three of them as small submucosal tumors. There was one plexiform schwannoma in the sigmoid composed of multiple nodules of prominently palisading schwann cells similar to those seen in conventional soft tissue schwannomas. All tumors studied were strongly positive for S-100 protein and also for low affinity nerve growth factor receptor (p75), collagen IV, and GFAP. Three tumors had CD34-positive cells, but all were negative for CD117 (KIT), neurofilament proteins, smooth muscle actin, and desmin. The percentage of MIB-1-positive cells was usually less than 1% and never higher than 3%. Colorectal schwannomas behaved in a benign fashion with no evidence of aggressive behavior or connection with neurofibromatosis 1 or 2, based on follow-up information on 18 patients.