The occurrence of double primary cancer of the esophagus and duodenum is considered to be very rare. Moreover, it is difficult to manage this type of double cancer because esophageal cancer has a biologic tendency towards early metastasis. Yet the development of endoscopy such as endoscopic ultrasonography (EUS), the new diagnostic imaging modalities such as PET/CT and advanced pathologic interpretation can lead to an early diagnosis of these multiple primary neoplasms. Appropriate intervention with various therapeutic tools then becomes possible, so these multiple primary neoplasms are not currently obstinate problems. We experienced one patient with double primary cancer; we simultaneously found esophageal cancer and duodenal cancer via endoscopy, and we wanted to treat them with chemo- radiation therapy and endoscopic submucosal dissection, but we failed to persuade the patient to accept the treatment. (Korean J Gastrointest Endosc 2008;37:413-418)