This review summarizes some of the common diagnostic problems encountered by pathologists when evaluating patients with chronic colitis and in whom inflammatory bowel disease (IBD) is either suspected or within the differential diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of ‘indeterminate colitis’ (IC). However, other reasons why pathologists may entertain a diagnosis of IC include failure to recognize or accept certain ‘hardcore’ histological features as indicative of CD, an attempt to classify cases of chronic colitis based on mucosal biopsy material or in the absence of adequate clinical and radiographic information, and the presence of other disease processes that mask, or mimic, IBD. In addition, some cases of UC may show unusual CD-like features, such as discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis and diversion colitis may, on occasion, also show IBD-like changes. The clinical and pathological features that aid in the distinction between these entities, and others, are covered in detail in this review.