Histology is a centerpiece in the diagnostic mosaic of small bowel diseases. This chapter discusses obtaining, processing, staining, and microscopic evaluation of small bowel biopsies. Some diagnoses are difficult to make on biopsies alone, e.g. in transmural diseases or of larger tumors where histology is rather performed on resected specimen to reach a final diagnosis. Although many small bowel diseases can be diagnosed histologically on formalin-fixed biopsies stained with Hematoxylin & Eosin, often additional staining methods and immunohistological stainings for specific antigens are required. Examples of biopsies in small bowel diseases with villous atrophy, ulceration, vasculitis, polyps, tumors, and storage diseases are presented, as well as links to cases with resected specimen. Optimal patients’ management in a multidisciplinary team approach is based on providing the pathologist with comprehensive clinical and endoscopic data, and finally a standardized pathological report is followed by individual discussion of equivocal cases.