Any disease that leads to impaired bile flow or impaired bile salt metabolism results in cholestasis. There are several causes of the disease related to intrahepatic or extrahepatic anatomical locations, to whether the disease is acute or chronic, to whether or not hepatocellular damage occurs, and to whether or not the condition is primary or secondary. The large number of entities that must be considered in the differential diagnosis of cholestatic diseases poses a major diagnostic challenge for both the clinician and the pathologist (1). This article establishes a diagnostic approach based on histologic patterns which emphasizes adult chronic cholestatic diseases. The next article will focus on the pediatric population