The presence of hyperferritinemia has to rule out acquired causes such as chronic inflammatory disorders, hemolytic anemia, liver diseases as hepatitis B or C, alcohol abuse and non alcoholic fatty liver disease, specially in patients with normal transferrine saturation. Genetic testing for hemochromatosis is systematically indicated in all patients with elevated transferrine saturation. When an iron overload is demonstrated in the absence of these classic causes, second-line genetic testing should be considered to exclude non HFE hemochromatosis. The aim of this paper is to propose a practical algorithm in the diagnosis of hyperferritinemia and to precise the diagnostic and therapeutic management of genetic hemochromatosis.