The differential diagnosis of idiopathic inflammatory bowel disease by colorectal biopsy poses a challenge to the endoscopist as well as the pathologist. Distinguishing non-idiopathic colitis from idiopathic colitis is the fundamental first step. No single histopathologic feature distinguishes between non-idiopathic and idiopathic inflammatory bowel disease or between the two forms of idiopathic inflammatory bowel disease (ulcerative colitis and Crohn's disease involving the colon). Interaction between the endoscopist and pathologist is essential in optimizing the contribution of colorectal biopsy to management of patients with inflammatory bowel disease.