Background Breast nonmass lesions (NMLs) are observed at screening and diagnostic US. However, knowledge is limited on imaging features of NMLs at screening US. Purpose To identify features of NMLs at screening US that are suspicious for malignancy based on mammographic findings. Materials and Methods This retrospective, multicenter study included asymptomatic women who underwent screening US between January 2012 and December 2019. Eligible women had NMLs at US, concurrent screening mammography, and record of a final diagnosis. Logistic regression analyses were used to identify factors associated with malignancy. The diagnostic performance of each sonographic feature according to mammographic findings was calculated. A reader study was performed to assess interreader agreement for sonographic features. Results Among 993 NMLs in 993 patients (mean age, 50 years ± 9 [SD]), 914 (92.0%) were benign and 79 (8.0%) were malignant. Mean size was larger for malignant NMLs than for benign NMLs (2.6 cm ± 1.1 vs 1.9 cm ± 0.8; P < .001). In multivariable analysis, associated calcifications (odds ratio [OR], 21.6 [95% CI: 8.0, 58.2]; P < .001), posterior shadowing (OR, 6.9 [95% CI: 2.6, 18.4]; P < .001), segmental distribution (OR, 6.2 [95% CI: 2.7, 14.4]; P < .001), mixed echogenicity (OR, 5.0 [95% CI: 1.8, 14.0]; P < .001), and size (OR, 1.5 [95% CI: 1.1, 2.1]; P = .01) at US were associated with malignancy. Associated calcifications, posterior shadowing, segmental distribution, and mixed echogenicity showed positive predictive values (PPVs) of 44%, 22%, 22.9%, and 16.6%, respectively. Having a negative mammogram was associated with a lower malignancy rate (2.8% vs 28.8%) and lower PPVs for sonographic features (0.7%-10.4% vs 24%-55%) than having a positive mammogram. Interreader agreement for sonographic features was good to excellent (Fleiss κ 95% CI lower bound range, 0.63-0.81). Conclusion Calcifications, posterior shadowing, segmental distribution, and mixed echogenicity associated with NMLs can be considered suspicious features for malignancy at screening US. As malignancy rates and PPVs differ according to mammographic abnormalities, combined assessment is mandatory. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grimm in this issue.