Often clinical symptoms and first investigations arouse the suspicion of inflammatory bowel disease. However, clinical features, such as diarrhoea, abdominal pain, or rectal bleeding, are not specific for either Crohn’s disease (CD) or ulcerative colitis (UC). As no single diagnostic criterion exists for inflammatory bowel disease (IBD) and several other diseases can mimic CD or UC, accurate patient profiling is needed to establish the final diagnosis. This includes patient history, endoscopic assessment, laboratory investigations, and radiologic examinations such as ultrasound or magnetic resonance imaging (MRI). The differential diagnosis varies with the type of symptoms, site of involvement, and the duration of symptoms and includes conditions such as irritable bowel syndrome, colon cancer, celiac disease, and infectious disorders, but also rare entities such as auto-immune enteropathy.