BACKGROUND Colonoscopy has an established role in reducing the burden of colorectal cancer through early detection and removal of polyps. For endoscopically unresectable polyps, colectomy is generally indicated to prevent malignant transformation or to remove cancer already present. OBJECTIVE This study aimed to determine the incidence of malignancy and the factors predictive of malignancy in surgically resected benign polyps. DESIGN/PATIENTS/SETTING: This study was a retrospective chart review of patients undergoing a colectomy for a colonic polyp (no preoperative diagnosis of cancer) in 4 hospitals within the Mayo Clinic Health System. MAIN OUTCOME MEASURES Patient characteristics, endoscopic location and size, and preoperative and operative polyp pathology were tabulated. Correlations between these features and the finding of invasive carcinoma on surgical pathology were assessed. RESULTS A total of 750 patients met our inclusion criteria. Patients were predominantly male (55.2%) with an average age of 69.4 ± 9.8 years. A majority of polyps were located in the right colon (70.9%). Invasive cancer was identified in 133 patients (17.7%). Multivariate analysis revealed polyps in the left colon (adjusted OR 2.13, 95% CI (1.22-3.72)), and those with high-grade dysplasia (adjusted OR 4.60, 95% CI (2.91-7.27)) were more likely to harbor carcinoma. Age, sex, polyp dimension, and villous features were not predictive of malignancy. Of the patients with cancer, 31 (23.3%) had nodal disease. LIMITATIONS This study is limited by its retrospective nature, the change in terminology and technique over time, and the partially subjective nature of an endoscopically unresectable polyp. CONCLUSIONS The finding that polyp size and villous features do not strongly predict malignancy differs from previous endoscopic studies. This study confirms that polyps located in the left colon or with high-grade dysplasia are more likely to harbor cancer. The results of this study suggest that endoscopically unresectable polyps are best treated by radical oncologic resection.