Proposal of an algorithm for the diagnosis of HC, from clinical/biochemical and imaging studies to molecular confirmation. Important note: in Whites, HFE genotyping is indicated with the specific purpose of detecting p.Cys282YTyr homozygosity (homoz.) and, if confirmed, to recommend appropriate preventive treatment by phlebotomies. Asian, African, and Native American subjects with defined HC phenotype could be directly referred to second-level genetic testing. In populations with a frequent component of Northern European ancestry, such as African Americans and Hispanics, there may still be a role for HFE genetic testing.