Diagnosis of inflammatory bowel disease (IBD) is complicated and is based on a combination of patient history and physical examination in association with laboratory, endoscopic, histologic, and radiographic investigations. Determination of the correct diagnosis is important for its implications in selecting treatment and in the timing and type of surgery that may be required. Information from testing incorporating serologic, genetic, and inflammatory markers can help to clarify the clinical picture. Measurement of biomarkers not only helps to differentiate a diagnosis of IBD versus non-IBD, it can also help to distinguish between ulcerative colitis and Crohn's disease in difficult cases. In this monograph, 5 cases illustrate how specialized testing can provide important information that can aid in diagnosis.