Small bowel cancer (SBC) is a rare entity that is increasing in incidence in the past few decades. The diagnosis of small intestinal tumors is often a challenge due to the rarity and diversity of these lesions, in addition to the variable and the nonspecific presenting signs and symptoms. Consequently, a majority of these tumors are discovered at a late stage with meager available therapeutic interventions. Small intestinal tumors arise from different histological lineages; epithelial cells (e.g. adenomas, adenocarcinomas, and carcinoids), mesenchymal cells (e.g. sarcomas and gastrointestinal stromal tumors) or from lymphatic tissues (e.g. lymphomas). In addition, the small intestine can be the site of distant metastasis of other malignancies. This chapter will cover epidemiology, pathogenesis, risk factors, clinical presentation, diagnosis, intestinal lymphoma, gastrointestinal stromal tumor and other mesenchymal tumors. Small bowel tumors are amongst the rarest types of cancer accounting for only 2% of all gastrointestinal cancers. Every year, there are approximately 6100 new cases of small bowel tumors with 1100 death cases per year in the USA. The National Cancer Institute estimates 6230 new cases for the year 2009 in the USA, with a corresponding 1110 deaths. SBC accounts for much lower incidence than colorectal, gastric or pancreatic malignancies. The natural history and prognosis of patients with SBC varies with different histological subtypes, with approximately overall survival of 50% for all types. Small bowel cancer is a rare, yet increasing disease. Diagnosis may be difficult due to the nonspecificity of the symptoms and hence clinical suspicion is key to diagnosis. Carcinoids of the small bowel are increasing and may be the most common malignancy of the small bowel, if not an equal share-holder of tumors to adenocarcinoma. Lymphomas are common tumors in the small bowel and may present with perforation. GISTs should be differentiated from leiomyomas and leiomyosarcomas and they possess malignant potential.