In the last several decades, the incidence of CD has been rising. This trend in part has been due to the clinical recognition of isolated CD. The differentiation can usually be made based on careful clinical history, physical examination, and diagnostic testing. The most reliable, sensitive method for differentiating these two diagnoses is colonoscopy. The ability to obtain directed endoscopic colonic biopsy specimens gives an even greater diagnostic yield. In many situations, observation of the clinical course and repeated diagnostic evaluations result in further clarification of the disease process involved. The importance of establishing an accurate diagnosis becomes most relevant when surgery is indicated. Once surgery has been performed, evidence of recurrent disease at the site of an ileostomy, ileal pouch, or ileorectal anastomosis establishes the disease as CD. In the absence of recurrent disease after colectomy, the difference becomes one of academic interest.