Background: Skin cancer is the most common cancer in the United States. Increasing evidence suggests that screening for malignant melanoma is effective, but its cost-effectiveness has not been determined. Objective: We attempted to determine the effectiveness and costs of a visual screen to diagnose malignant melanoma in high-risk persons. Methods: We developed a decision analysis comparing no skin cancer screen with a single screen by a dermatologist. Clinical outcomes included malignant melanoma, nonmelanoma skin cancer, or no skin cancer. Life expectancy and costs of care were projected on the basis of clinical findings. Results: Skin cancer screening increased average discounted life expectancy from 15.0963 years to 15.0975 years. Based on the prevalence of malignant melanoma, however, this translates into an increased discounted life expectancy of 0.9231 years for each person with diagnosed melanoma. Using a cost of $30 per screen, total skin cancer–related costs for a cohort of 1 million people increased from $826 million with no screen to $861 million with screening, with an increase of 1200 years of life. This results in an incremental cost-effectiveness ratio of $29,170 per year of life saved (YLS) with screening. Sensitivity analysis showed that the cost-effectiveness ratio for screening remained below $50,000/YLS if the prevalence of melanoma in the screened population was at least 0.0009, the probability that a melanoma detected in screening was localized was at least 94.8%, or the cost of each screen was below $57. Conclusion: Skin cancer screening in high-risk patients is likely to be associated with a small increase in discounted life expectancy and is reasonably cost-effective compared with other cancer screening strategies. (J Am Acad Dermatol 1999;41:738-45.)