Essentially a clinical diagnosis, classically the term hemochromatosis has denoted iron storage disease of varying etiology accompanied by tissue damage. Common pathologic manifestations are cirrhosis of the liver, diabetes, darkening of the skin and cardiac arrhythmias and failure. The cause can be hereditary, as in the HLA-linked form most common in Europeans, or acquired, as the result of transfusions and/or disordered erythropoiesis as in thalassemia. With the positional cloning of the HFE gene, the term hemochromatosis has been increasingly taken to represent an HFE genotype, with or without pathologic changes.