Duodenal gastrointestinal stromal tumors (GISTs) are relatively rare tumors that commonly present with gastrointestinal bleeding. Evaluation with endoscopic ultrasonography (EUS) is a useful technique for the differential diagnosis of GISTs from other submucosal tumors. A 58-year-old man presented with melena and anemia. An esophago-gastroduodenoscopy showed the presence of a submucosal tumor in the second portion of the duodenum with central ulceration and a flat spot. EUS showed the presence of a suspicious malignant GIST that originated from the proper muscle layer, which was successfully resected. We report a case of a duodenal GIST with a bleeding ulcer. Positive reactivity for CD117 and S-100 was demonstrated by immunohistochemical staining. (Korean J Gastrointest Endosc 2009;39:42-45)