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Purpose To determine the interval cancer rate (ICR) after negative screening contrast-enhanced mammography (CEM) and compare the characteristics of interval cancers (ICs) with those of CEM screen-detected cancers. Materials and Methods This retrospective, single-institution study included consecutive screening CEM examinations performed from January 2015 through December 2021. ICs diagnosed within 1 year of a negative screening CEM and all CEM screen-detected cancers were identified. Two breast radiologists independently reviewed prior negative CEM examinations to classify ICs as missed, misinterpreted, or occult. Patient- and lesion-level characteristics were compared between ICs and screen-detected cancers using the Wilcoxon rank sum test for continuous variables and the Fisher exact or χ² tests for categorical variables. Results The study included 6911 screening CEM examinations in 2756 female patients (median age, 53 years; IQR, 47-60 years). Among 6120 negative screening examinations, 14 ICs were diagnosed in 14 patients. The overall ICR was 2.29 cancers per 1000 examinations, and the symptomatic ICR was 0.82 per 1000 examinations (five of 6120). ICs accounted for 13% (14 of 106) of all cancers diagnosed (interval and screen detected). Invasive ICs occurred more frequently in the setting of moderate or marked background parenchymal enhancement than screen-detected cancers (six of eight, 75% vs 17 of 57, 30%; P = .02). Most ICs (10 of 14, 71%) were occult on prior screening CEM. Conclusion The ICR after CEM was 2.29 cancers per 1000 examinations, representing 13% of all cancers diagnosed. Most ICs were occult at prior CEM, and invasive ICs were more frequently associated with moderate or marked background parenchymal enhancement when compared with CEM screen-detected cancers. Keywords: Mammography, Breast, Interval Cancers Supplemental material is available for this article. © RSNA, 2026.