Granular cell tumor (GCT) is commonly located in the subcutaneous tissue and oral cavity, and uncommon in the gastrointestinal tract, in which the majority arises in the esophagus with over-representation in African Americans (AA). However, experience with GCTs of the colorectum is quite limited. We report the clinicopathologic features of 1 of the largest series to date of colorectal GCTs. We reviewed the clinical features of 26 colorectal GCTs seen at our institution between the years 1995 to 2009, which included 24 biopsies, 1 low anterior resection, and 1 colectomy. Review of the clinical features of all 26 cases from 24 patients identified an equal gender distribution (12 males and 12 females), with patients ranging in age from 31 to 60 years (mean, 49.8 y; median, 51.5 y) with a modest White predominance (15/24, 63%; our overall patient population is 67% White). The majority of colorectal GCT involved the right colon (19/26, 73%) ranging in size from 0.2 to 1.8 cm (mean 0.6 cm). Most neoplasms were encountered on routine colonoscopy (14/24, 64%), however 3 patients presented with hematochezia, 3 with changing bowel habits, 2 with Crohn disease, 1 with diverticular disease, and 1 with appendicitis. Of the 20 cases available for histologic review, the tumors were noted to either be infiltrative (12/20, 60%) or marginated (8/20, 40%) involving either the mucosa (7/20, 35%), submucosa (10/20, 50%), or both (3/20, 15%). The microscopic features were similar to those of GCTs found elsewhere, but many of the neoplasms differed by displaying nuclear pleomorphism (8/20, 40%), lymphoid cuffs (9/20, 45%), and focal calcification (7/20, 35%). Some had reactive mucosal surface changes (7/20, 35%), including 1 initially misdiagnosed as a tubular adenoma. Neither mitoses nor necrosis were identified. On immunochemistry, 18 of the neoplasms were stained for S-100 and all cases showed positive staining. Follow-up information was available for 19 patients (19/24, 79%) with 2 documented occurrences of regrowth at the prior cecal biopsy site owing to incomplete excision, but no metastases. Although infrequently found in the colorectum, colorectal GCT typically presents incidentally on routine colonoscopy and involves the right colon; it is not over-represented in AA patients. GCTs can have both an infiltrative or marginated growth pattern with a subset displaying nuclear pleomorphism, a lymphoid cuff, focal calcification, and reactive mucosal surface changes, which in our experience, may lead to misdiagnosis on colorectal mucosal biopsies. Although GCTs were benign tumors in this series, if incompletely excised regrowth of the lesion may occur and therefore, follow-up may be warranted.