This report describes four siblings affected with familial intrahepatic cholestasis detected in early infancy. In the two male siblings, biliary cirrhosis and fatal hepatocellular carcinoma later developed, whereas the female siblings have had persistent hepatomegaly and recurrent episodes of cholestasis. Sequential biopsies show that this rare disorder of unknown etiology must be added to the many causes of giant cell transformation of the liver in infancy. Its oncogenic risk, particularly in males, has not been generally appreciated.