Hyperplastic polyps are the most frequent nonneoplastic lesions of the colon. Typically, they are small sessile polyps (5 mm) located in the rectosigmoid area. Recently, they have been identified as markers of neoplastic polyps. Herein we describe four cases of large (20 mm in size) hyperplastic polyps found at our institution over a 9-year period. All four polyps were excised by endoscopic polypectomy on an outpatient basis without complications. Two polyps were in the right colon; one was pedunculated, none of them was associated with synchronous neoplastic polyps or polyposis. Up to now, follow-up in three patients has been negative for metachronous polyps. We conclude that a large hyperplastic polyp is an unexpected and rare finding, difficult to distinguish, and not related to particular colonic sites or synchronous adenomatous lesions. These polyps should be removed with a standard technique, and patients need to be followed with successive endoscopies.