The Norwegian Breast Cancer Screening Programme (NBCSP) has a nation-wide coverage since 2005. All women aged 50–69 years are invited biennially for mammography screening. We evaluated breast cancer mortality reduction and performed a cost-effectiveness analysis, using our microsimulation model, calibrated to most recent data. The microsimulation model allows for the comparison of mortality and costs between a (hypothetical) situation without screening and a situation with screening. Breast cancer incidence in Norway had a steep increase in the early 1990s. We calibrated the model to simulate this increase and included recent costs for screening, diagnosis and treatment of breast cancer and travel and productivity loss. We estimate a 16% breast cancer mortality reduction for a cohort of women, invited to screening, followed over their complete lifetime. Cost-effectiveness is estimated at NOK 112,162 per QALY gained, when taking only direct medical costs into account (the cost of the buses, examinations, and invitations). We used a 3.5% annual discount rate. Cost-effectiveness estimates are substantially below the threshold of NOK 1,926,366 as recommended by the WHO guidelines. For the Norwegian population, which has been gradually exposed to screening, breast cancer mortality reduction for women exposed to screening is increasing and is estimated to rise to ∼30% in 2020 for women aged 55–80 years. The NBCSP is a highly cost-effective measure to reduce breast cancer specific mortality. We estimate a breast cancer specific mortality reduction of 16–30%, at the cost of 112,162 NOK per QALY gained.