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Objective: Digital breast tomosynthesis (DBT) has significantly improved cancer detection capabilities through its identification of subtle findings often imperceptible on 2D digital mammography, particularly architectural distortion (AD). The purpose of this study was to analyze of suspicious AD detected on screening DBT to evaluate the incidence of malignancy and to determine other patient or imaging characteristics in these cases as possible predictors of malignancy. Methods: This was an IRB approved retrospective analysis of subjects with AD detected on DBT screening mammography who were given a biopsy recommendation between January 1, 2016, and June 30, 2018. Univariate analysis of various imaging characteristics and patient high-risk factors was performed for statistical correlation with diagnosis of malignancy. Results: In the 218 DBT-detected AD findings with a final BI-RADS assessment of 4 or 5 on diagnostic workup, 94 (43.1%) yielded malignancy, 57 (26.2%) were classified as high-risk, and 67 (30.7%) were benign. There was a strong statistically significant association with malignancy in the cases with an US correlate (P < 0.0001). There was a statistically significant inverse correlation between malignancy and one-view findings (P = 0.0002). The presence of AD on 2D (P = 0.005) or synthetic 2D views (P = 0.002) showed statistically significant correlations with malignancy, whereas breast density or high-risk factors (P = 0.316) did not. Conclusion: AD detected on DBT that persists on further workup and has no explainable cause should be considered suspicious for malignancy. Identification of the AD on both standard mammographic views and the presence of an US correlate significantly increase the probability of malignancy. [ABSTRACT FROM AUTHOR]