The American Cancer Society Guidelines (ACS) recommends women at average risk for breast cancer to begin annual mammography at age 40. OBJECTIVE: To develop a preliminary model to evaluate the cost-effectiveness of these guidelines, using similar assumptions and clinical trial evidence sources for the breast cancer mortality benefit as the ACS. METHODS: Interventions: Annual mammography until age 70 vs. no annual mammography. Design: Age-specific discounted lifetime costs and discounted quality-adjusted life expectancy were estimated for each intervention, and the incremental cost-effectiveness ratio (ICER) calculated. Life-expectancy estimates were generated by Markov model simulation starting from age 40. Direct costs included the management of early-stage and invasive breast cancer, and the costs of mammography and the workup of a positive result. Indirect costs accounted for the time spent getting mammograms. BC management costs with and without mammography were assumed to be the same. Time Horizon: Lifetime. Perspective: Societal. Target Population: The model was estimated in white females aged 40 and over. Data Sources: RCT Meta-analysis evidence sources used by the ACS, SEER data for BC mortality and life expectancy, NCHS life-tables data, studies of mammography performance, and quality of life/health utility studies. Sensitivity analysis was done to the discount rate, costs, sensitivity of mammography and costs of mammography. RESULTS: Base-Case Analysis: The ICER for annual mammography until age 70 was extremely high with a minimum value of $347,442/QALY at age 60. Annual mammography until age 80 was slightly more cost-effective, ranging from $424,058/QALY, $323,893/QALY and $271,773/QALY at ages 40, 55, and 70 respectively. CONCLUSIONS: Annual mammography starting from age 40 may turn out to be a very expensive policy. However, the economic model has some limitations: the mammography intervention may be associated with different BC management costs; and the data sources for BC mortality reduction with mammography have been widely disputed.