Brunner’s gland hamartoma (BGH) is an uncommon benign tumor arising from alkaline-based mucin-secreting glands of the duodenum. These lesions are typically discovered incidentally during upper gastrointestinal endoscopy or radiological diagnostics, even though they can eventually lead (in the case of increasing size) to obstructive or hemorrhagic symptoms. We report the case of a 67-year-old Caucasian man with two episodes of melena and epigastric pain during the last month. Esophagogastroduodenoscopy revealed a large pedunculated and eroded polyp inside the antrum with a 2-cm-long stalk arising from the anterior wall of the duodenal bulb. Endoscopic ultrasonography showed a submucosal lesion with homogeneous hyperechoic parietal thickening and some central gaps. The muscularis was undamaged. No lymphadenopathy was observed. We performed an en bloc endoscopic resection of the polyp. The size of the whole piece was approximately 6 × 3 × 2 cm, pseudocapsulated and tough in consistency. In the case presented, the en bloc endoscopic removal was successful despite the size of the tumor.