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The effectiveness of cancer screening is a salient health policy issue that remains unresolved. This article sheds new light on the benefits of population-wide cancer screening. We investigate changes in mortality after the introduction of screening guidelines for breast and prostate cancers in the USA and UK. We use differences in the timing of guideline adoption, differences in ages recommended for screening, and differences in which cancers are detectable by screening to identify the effect of cancer screening guidelines. Our quadruple-differencing strategy finds a moderately sized mortality benefit from mammography and prostate-specific antigen (PSA) screening guidelines among recommended age groups and little change in mortality rates among age groups not recommended to receive screening. As a falsification test, we verify that prostate cancer rates among men did not fall after the introduction of mammography screening and breast cancer rates among women did not fall after the introduction of the PSA test. [ABSTRACT FROM AUTHOR]