Background There is little information on the individual risk of screen-detected cancer in women over successive participations. This study aimed to estimate the 10-year cumulative breast cancer detection risk (ductal carcinoma in situ and invasive carcinoma) in a populationbased breast cancer screening program according to distinct protocol strategies. A further aim was to determine which strategies maximized the cancer detection risk and how this risk was affected by the radiologic protocol variables. Methods Data were drawn from a retrospective cohort of women from nine population-based screening programs in Spain from 1990 to 2006. We used logistic regression with discrete intervals to estimate the cumulative detection risk at 10 years of follow-up according to radiologic variables and protocol strategies. Results In women starting screening at the age of 45–59 years, the cumulative risk of screen-detected cancer at 10 years ranged from 11.11 to 16.71 per 1,000 participants according to the protocol strategy. The cumulative detection risk for overall cancer and invasive cancer was the highest with strategies using digital mammography, double reading, and two projections (16.71 and 12.07 %, respectively). For ductal carcinoma in situ, cumulative detection risk was the highest with strategies using screen-film, double reading, and two projections (2.32 %). The risk was the lowest with strategies using screen-film mammography, single reading, and two projections. Conclusions This study found that at least eleven cancers are detected per 1,000 women screened in the first 10 years of follow-up. Enhanced knowledge of the variability in cumulative risk of screendetected cancer could improve protocol strategies.