OBJECTIVES: This study examines screening alternatives for detection of hereditary hemochromatosis (HH). The objectives included: (1) To evaluate three screening alternatives (no screening, phenotype screening, and genotype screening) in a cost-effectiveness analysis for HH; and, (2) To serve as a model for genetic diseases. METHODS: The decision analysis using Data 3.5 software was conducted for both cost-effectiveness and cost-utility analyses. A hypothetical cohort of 10,000 white males between thirty and thirty-nine years old was the identified as the model population because of its high HH prevalence rate. Each screening alternative correlated to a decision tree branch, which further subdivided into branches depending upon treatment decisions. The costs data were conservatively estimated using 2001 United States Medicare charge data. Testing protocols were based on established methods previously used in a cost-effectiveness study by Adams and Valberg in 1999. The utility values were estimated using experts' judgments on the Health Utilities Index. RESULTS: The results of the cost-effectiveness analysis indicated that genotype testing was the dominant strategy. The marginal cost-effectiveness of genetic testing found that an extra $219.85 per case would identify another thirteen cases. A sensitivity analysis found the genetic testing cost as the threshold value. The cost-utility analysis, using quality-adjusted life years (QALY) as a measure of effectiveness, indicated that genotype testing was the dominant strategy. The marginal cost/QALY found that an additional $85.48 per case identified 10 new cases. CONCLUSIONS: Genetic testing for HH represents an opportunity for widespread screening. The high prevalence rate and benefit of early diagnosis and treatment make HH an ideal screening target. The infrastructure for genetic testing must be built before widespread screening could occur; thus, the policy-makers and insurance companies should be educated about cost-effectiveness studies which demonstrate the merits of detecting genetic diseases prior to symptom manifestation.