Background: Although breast cancer is the most common cancer in women, economic evaluation of breast cancer screening is not fully addressed in developing countries. The main objective of the present study was to analyze the cost-effectiveness of breast cancer screening using mammography in 35-69 year old women in an Iranian setting. Materials and Methods: This was an economic evaluation study assessing the cost-effectiveness of a population-based screening program in 35-69 year old women residing in rural areas of South east Iran. The study was conducted from the perspective of policy-makers of insurance. The study population consisted of 35- to 69-year old women in rural areas of Kerman with a population of about 19,651 in 2013. The decision tree modeling and economic evaluation software were used for cost-effectiveness and sensitivity analyses of the interventions. Results: The total cost of the screening program was 7,067.69 US$ and the total effectiveness for screening and no-screening interventions was 0.06171 and 0.00864 disability adjusted life years averted, respectively. The average cost-effectiveness ratio DALY averted US$ for screening intervention was 7,7082.5 US$ per DALY averted and 589,027 US $ for no-screening intervention. The incremental cost-effectiveness ratio DALY averted was 6,264 US$ per DALY averted for screening intervention compared with no-screening intervention. Conclusions: Although the screening intervention is more cost effective than the alternative (noscreening) strategy, it seems that including breast cancer screening program in health insurance package may not be recommended as long as the target group has a low participation rate.