ObjectiveMammography and MRI screening typically occur in combination or in alternating sequence. We compared multimodality screening performance accounting for the relative timing of mammography and MRI and overlapping follow-up periods. MethodsWe identified 8,260 screening mammograms performed 2005 to 2017 in the Breast Cancer Surveillance Consortium, paired with screening MRIs within ±90 days (combined screening) or 91 to 270 days (alternating screening). Performance for combined screening (cancer detection rate [CDR] per 1,000 examinations and sensitivity) was calculated with 1-year follow-up for each modality, and with a single follow-up period treating the two tests as a single test. Alternating screening performance was calculated with 1-year follow-up for each modality and also with follow-up ending at the next screen if within 1 year (truncated follow-up). ResultsFor 3,810 combined screening pairs, CDR per 1,000 screens was 6.8 (95% confidence interval [CI]: 4.6-10.0) for mammography and 12.3 (95% CI: 9.3-16.4) for MRI as separate tests compared with 13.1 (95% CI: 10.0-17.3) as a single combined test. Sensitivity of each test was 48.1% (35.0%-61.5%) for mammography and 79.7% (95% CI: 67.7%-88.0%) for MRI compared with 96.2% (95% CI: 85.9%-99.0%) for combined screening. For 4,450 alternating screening pairs, mammography CDR per 1,000 screens changed from 3.6 (95% CI: 2.2-5.9) to zero with truncated follow-up; sensitivity was incalculable (denominator = 0). MRI CDR per 1,000 screens changed from 12.1 (95% CI 9.3-15.8) to 11.7 (95% CI: 8.9-15.3) with truncated follow-up; sensitivity changed from 75.0% (95% CI 63.8%-83.6%) to 86.7% (95% CI 75.5%-93.2%). DiscussionUpdating auditing approaches to account for combined and alternating screening sequencing and to address outcome attribution issues arising from overlapping follow-up periods can improve the accuracy of multimodality screening performance evaluation.