Neonatal hemochromatosis is a specific entity in the spectrum of pediatric liver disease. The clinical course is characterized by progressive deterioration, leading to death within a few days to weeks. The pathologic changes are hepatic fibrosis with massive iron accumulation in hepatocytes. Lesser amounts of iron are found in parenchymal cells of the endocrine organs (adrenal, thyroid, pancreas, pituitary), the heart, and renal tubules. Little iron is present in cells of the reticuloendothelial system. The morphologic pattern thus resembles that of adult idiopathic hemochromatosis. Iron accumulation is a relatively specific finding, as shown by a review of a series of pediatric autopsy cases. Premortem diagnosis of this disease has been made only rarely, and little information is available on laboratory parameters. Recognition of this entity in living neonates is necessary for better understanding of its pathogenesis and treatment.