OBJECTIVES: Study costs of carrying out a genetic screening programme per 100.000 individuals from the Spanish population under 30 years of age for Hereditary Hemochromatosis (HH), based on the calculated penetrance of HH in the South-West Healthcare Area 11 of Madrid, and the published prevalence of the HH genotype in Spain. METHODS: Retrospective cross-sectional study of HFE genotyping requests from a subpopulation in South West Madrid pre-screened for high ferritin values, between January 2000 and June 2006. Based on  our population’s genotype and phenotype, clinical penetrance was calculated in a previous study. Costs, extracted from a Spanish Medical Cost database (SOYKOS), involved in treatment of HH-associated diseases, biochemical testing, genetic testing, treatment of phenotypical HH patients and follow up were analysed to compare the costs for genetic screening versus no screening. RESULTS: From our data, for the main HH-associated diseases, we have previously calculated a clinical penetrance, for HH genotype, in the population studied, of 1.11%, compared to 0.08% for those with wild-type HFE genotype. The main HH-associated pathologies considered are hepatopathy, diabetes and arthropathy. Cost for genetic testing of 100,000 Spanish individuals under 30 years of, biochemical follow up of those with HH genotype, and treatment of those with HH genotype and phenotype amounts to €1,808,353.29, equivalent to €1433.49/case with HH genotype detected and €129,168.09 per phenotypical case with HH genotype detected. Treatment of HH-associated pathologies, if no other preventive intervention is undertaken (biochemical monitoring, preventive phlebotomy treatment), would cost €407,043.70. CONCLUSIONS: The extremely low penetrance of HH-associated pathologies related to the HH genotype, suggests that a genetic screening programme for the population proposed is not economically justified for the Spanish National Healthcare System. However, this does not exclude genetic screening of first degree relatives of HH patients and their subsequent biochemical follow-up which could prove to be appropriate.