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Small bowel adenocarcinoma is a clinically and anatomically distinct gastrointestinal cancer that lacks prospective data to support its optimal management. Patients with inflammatory bowel disease and inherited conditions that cause gastrointestinal polyps are at especially high risk. Due to a lack of effective surveillance programs resulting in missed or delayed diagnoses only when symptoms develop, this disease is generally discovered at an advanced stage. Surgical resection is the only treatment modality with a chance of cure. Currently accepted treatment considerations are often generalized from large bowel and pancreatic-biliary cancers, due to some anatomic and clinical parallels. Additional research, however, is desperately needed to characterize the unique molecular differences of this disease to better prognosticate patients and establish rational clinical trials that would improve their outcomes.