Objective: Radiomics and deep transfer learning are two popular technologies used to develop computer-aided detection and diadnosis (CAD) schemes of medical images. This study aims to investigate and compare advantages and potential limitations of applying these two technologies in developing CAD schemes. Methods: A relatively large and diverse retrospective dataset including 3,000 digital mammograms is assembled in which 1,496 images depict malignant lesions and 1,054 images depict benign lesions. Two CAD schemes are developed to classify breast lesions. The first scheme is developed using four steps namely, applying an adaptive multi-layer topographic region growing algorithm to segment lesions, computing initial radiomics features, applying a principal component algorithm to generate an optimal feature vector, and building a support vector machine classifier. The second CAD scheme is built based a pre-trained residual net architecture (ResNet50) as a transfer learning model to classify breast lesions. Both CAD schemes are trained and tested using a 10-fold cross-validation method. Several score fusion methods are also investigated to classify breast lesions. CAD classification performance is evaluated by the area under ROC curve (AUC). Results: ResNet50 model-based CAD scheme yields AUC = 0.85±0.02, which is significantly higher than radiomics feature-based CAD scheme with AUC = 0.77±0.02 (p < 0.01). Additionally, fusion of classification scores generated by two CAD schemes does not further improve classification performance. Conclusion: This study indicates that using deep transfer learning is more efficient to develop CAD schemes and enables to yield higher lesion classification performance than CAD schemes developed using radiomics-based technology.