The patterns and incidences of orcein-positive granules of copper-binding protein (CBP) in 2,531 liver biopsy specimens from children and adults with a large variety of liver diseases are reported. Fetal and neonatal livers have high physiologic levels of copper and CBP, which fall to within the adult range by the third to the sixth month of life. Therefore, in liver specimens from children less than 6 months of age, it was not possible to determine whether the orcein-positive granules present represented physiologic or pathologic deposits of CBP. In adults and in children older than 6 months of age, CBP granules were found almost exclusively in association with four main groups of liver diseases: Wilson's disease, chronic biliary disorders, cirrhosis/extensive fibrosis, and primary liver tumors. Orcein-positive granules were never found in patients with acute liver disease. The granules were extremely helpful in distinguishing chronic biliary diseases from acute cholestatic and hepatic disorders, primary biliary cirrhosis from chronic active hepatitis, and primary liver tumors from metastatic tumor deposits.