Introduction: Service breast cancer screening is difficult to evaluate because there is no unscreened control group. Due to a natural experiment, where 20% of women were offered screening in two regions up to 17 years before other women, Denmark is in a unique position. We utilized this opportunity to assess outcome of service screening. Materials and methods: Screening was offered in Copenhagen from 1991 and Funen from 1993 to women aged 50–69 years. We used difference-in-differences methodology with a study group offered screening; a historical control group; a regional control group; and a regional–historical control group, comparing breast cancer mortality and incidence, including ductal carcinoma in situ, between study and historical control group adjusted for changes in other regions, and calculating ratios of rate ratios (RRR) with 95% confidence intervals (CI). Data came from Central Population Register; mammography screening databases; Cause of Death Register; and Danish Cancer Register. Results: For breast cancer mortality, the study group accumulated 1,551,465 person-years and 911 deaths. Long-term breast cancer mortality in Copenhagen was 20% below expected in absence of screening; RRR 0.80 (95% CI 0.71–0.90), and in Funen 22% below; RRR 0.78 (95% CI 0.68–0.89). Combined, cumulative breast cancer incidence in women followed 8+ years post-screening was 2.3% above expected in absence of screening; RRR 1.023 (95% CI 0.97–1.08). Discussion: Benefit-to-harm ratio of the two Danish screening programs was 2.6 saved breast cancer deaths per overdiagnosed case. Screening can affect only breast cancers diagnosed in screening age. Due to high breast cancer incidence after age 70, only one-third of breast cancer deaths after age 50 could potentially be affected by screening. Increasing upper age limit could be considered, but might affect benefit-to-harm ratio negatively.