Most histologic studies of cryptogenic chronic liver disease were done before the discovery of hepatitis C, and therefore encompass the histologic spectrum of this disease. The authors report the histopathologic findings of 18 liver biopsies of presumed cryptogenic chronic liver disease patients and compared them to chronic autoimmune hepatitis and hepatitis C virus biopsies. Severe bridging fibrosis or cirrhosis was present in 55%. Eighty percent of biopsies had minimal necroinflammatory activity including those with cirrhosis; 20% had moderate activity. Histologic distinction from chronic hepatitis C was difficult in the minimally active cryptogenic chronic liver disease biopsies because 20% of biopsies had portal lymphoid follicles and 33% had macrovesicular steatosis. Chronic autoimmune hepatitis had more parenchymal necroinflammatory activity and plasma cells than did either cryptogenic chronic liver disease or chronic hepatitis C biopsies. These findings suggest that one form of cryptogenic chronic liver disease is a persistent, low grade hepatitis that can progress to cirrhosis despite an innocuous histopathologic appearance. Pathologists should be aware that cryptogenic chronic liver disease biopsies may have minimal histologic abnormalities. These biopsies should not be reported as normal. Such cases require long-term clinical follow-up.