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We sought to develop new quantitative approaches to characterize the spatial distribution of mammographic density and contrast enhancement of suspicious contrast-enhanced mammography (CEM) findings to improve malignant vs. benign classifications of breast lesions. We retrospectively analyzed all breast lesions that underwent CEM imaging and tissue sampling at our institution from 2014–2020 in this IRB-approved study. A penalized linear discriminant analysis was used to classify lesions based on the averaged histograms of radial distributions of mammographic density and contrast enhancement. T-tests were used to compare the classification accuracies of density, contrast, and concatenated density and contrast histograms. Logistic regression and AUC-ROC analyses were used to assess if adding demographic and clinical data improved the model accuracy. A total of 159 suspicious findings were evaluated. Density histograms were more accurate in classifying lesions as malignant or benign than a random classifier (62.37% vs. 48%; p < 0.001), but the concatenated density and contrast histograms demonstrated a higher accuracy (71.25%; p < 0.001) than the density histograms alone. Including the demographic and clinical data in our models led to a higher AUC-ROC than concatenated density and contrast images (0.81 vs. 0.70; p < 0.001). In the classification of invasive vs. non-invasive malignancy, the concatenated density and contrast histograms demonstrated no significant improvement in accuracy over the density histograms alone (77.63% vs. 78.59%; p = 0.504). Our findings suggest that quantitative differences in the radial distribution of mammographic density could be used to discriminate malignant from benign breast findings; however, classification accuracy was significantly improved with the addition of contrast-enhanced imaging data from CEM. Adding patient demographic and clinical information further improved the classification accuracy.