Our ability to detect those predisposed to haemochromatosis is greatly enhanced by testing for HFE mutations. Ironically, this diagnostic advance has led to some confusion regarding the criteria for diagnosis of haemochromatosis, with overreliance on genetic testing instead of investigations for iron overload. Because many people who are homozygous for the C282Y mutation, or compound heterozygous for the C282Y and H63D mutations, either do not express or only partially express the disease, it is essential to confirm a diagnosis of haemochromatosis on the basis of increased body iron stores. Liver biopsy remains the best method of confirming this and has an important role in the patient with either borderline iron overload or advanced disease. Persistent elevation of serum ferritin concentration in the absence of overt liver damage, inflammation or neoplasia, and estimation of mobilized body iron by repeated phlebotomy, are reasonable alternatives to liver biopsy. Although the precise definition of iron overload is debated, a diagnosis of haemochromatosis cannot be made without demonstrating increased body iron stores.