Histological support for a diagnosis of inflammatory bowel disease (IBD) requires characteristic features, e.g. basal plasmacytosis, architectural changes, and granulomas. Unfortunately, many conditions share histological features with IBD. One of the closest mimics is diverticular colitis, a process that occurs adjacent or close to diverticula. It often resembles ulcerative colitis (UC), but, unlike UC, it rarely involves the rectum. Another close mimic is diversion proctocolitis, which is easy to diagnose if the history is available but otherwise is often difficult to distinguish from IBD. Mucosal changes similar to those of IBD may be the result of various infections, e.g. lymphogranuloma venereum/syphilis, amoebiasis, and HIV. Other causes include mass lesions and drugs. Granulomas are a feature of Crohn’s disease but can occur in other settings. In tuberculosis, they are typically larger and more confluent than in Crohn’s disease and may show necrosis. Rarer potential mimics of IBD include common variable immunodeficiency, Behçet’s disease, graft-versus-host disease, endometriosis, and pneumatosis coli. Close attention to the clinical picture and a careful approach to colorectal biopsy assessment by the pathologist should help reduce the chance of misdiagnosis and incorrect management.