This goal of this research was to evaluate the cost-effectiveness of the National Cancer Screening Program (NCSP) for breast cancer in the Republic of Korea from a government expenditure perspective. In 2002-2003 (baseline), a total of 8,724,860 women aged 40 years or over were invited to attend breast cancer screening by the NCSP. Those who attended were identified using the NCSP database, and women were divided into two groups, women who attended screening at baseline (screened group) and those who did not (non-screened group). Breast cancer diagnosis in both groups at baseline, and during 5-year follow-up was identified using the Korean Central Cancer Registry. The effectiveness of the NCSP for breast cancer was estimated by comparing 5-year survival and life years saved (LYS) between the screened and the unscreened groups, measured using mortality data from the Korean National Health Insurance Corporation and the National Health Statistical Office. Direct screening costs, indirect screening costs, and productivity costs were considered in different combinations in the model. When all three of these costs were considered together, the incremental cost to save one life year of a breast cancer patient was 42,305,000 Korean Won (KW) (1 USD=1,088 KW) for the screened group compared to the non-screened group. In sensitivity analyses, reducing the false-positive rate of the screening program by half was the most cost-effective (incremental cost-effectiveness ratio, ICER=30,110,852 KW/LYS) strategy. When the upper age limit for screening was set at 70 years, it became more cost-effective (ICER=39,641,823 KW/LYS) than when no upper age limit was set. The NCSP for breast cancer in Korea seems to be accepted as cost-effective as ICER estimates were around the Gross Domestic Product. However, cost-effectiveness could be further improved by increasing the sensitivity of breast cancer screening and by setting appropriate age limits.