A large number of blood-based markers have been proposed for early detection of colorectal cancer (CRC). Their sensitivity for detecting CRC has mostly been evaluated in clinical settings, and found to be higher in more advanced stages compared with earlier stages of the disease. The aim of this study is to estimate the overall sensitivity of blood-based markers expected in screening settings, where the proportion of advanced stages is typically lower than in clinical settings. A systematic literature review was performed on studies evaluating sensitivity and specificity of blood-based markers for early detection of CRC. For each study, overall sensitivity expected in screening settings was estimated by weighting stage-specific sensitivities according to the stage distribution of CRC expected in the screening setting. The latter was derived from 12,605 CRC cases diagnosed in the German screening colonoscopy program during 2003-2007. Overall, 73 studies evaluating 55 blood-based markers were identified. Adjusted sensitivity was lower than reported sensitivity in 120 (90%) evaluations of different markers. Median absolute reduction in sensitivity after adjustment was 9.0% (interquartile range: 4.0-13.0) units, whereas median relative reduction was 19.5% (interquartile range: 11.3-33.3%). Blood-based markers for CRC detection reported from clinical settings showed higher sensitivities than expected in the screening setting in most cases, mainly due to substantially higher proportions of advanced stage cancers. Adjustment of sensitivity to the stage distribution expected in the screening setting is crucial to obtain realistic and comparable estimates of sensitivities.