Crohn's disease and ulcerative colitis are distinct entities, but in 5 to 10% of patients and resected specimens, a clear separation may not be possible. The pathological diagnosis and differential diagnosis of Crohn's disease, including ulcerative colitis, indeterminate colitis and other diseases that may mimic Crohn's disease are discussed in this review, with particular emphasis on the biopsy diagnosis. It is often difficult or impossible to distinguish diversion colitis and pouchitis from recurrence of Crohn's disease; special measures need to be taken for their identification. The predisposition to cancer, and the presence of dysplasia in Crohn's disease in relation to surveillance, are also discussed.