Microcalcifications in breast tissue can be an early sign of breast cancer, and play a crucial role in breast cancer screening. This study proposes a radiomics approach based on advanced machine learning algorithms for diagnosing pathological microcalcifications in mammogram images and provides radiologists with a valuable decision support system (in regard to diagnosing patients). An adaptive enhancement method based on the contourlet transform is proposed to enhance microcalcifications and effectively suppress background and noise. Textural and statistical features are extracted from each wavelet layer’s high-frequency coefficients to detect microcalcification regions. The top-hat morphological operator and wavelet transform segment microcalcifications, implying their exact locations. Finally, the proposed radiomic fusion algorithm is employed to classify the selected features into benign and malignant. The proposed model’s diagnostic performance was evaluated on the MIAS dataset and compared with traditional machine learning models, such as the support vector machine, K-nearest neighbor, and random forest, using different evaluation parameters. Our proposed approach outperformed existing models in diagnosing microcalcification by achieving an 0.90 area under the curve, 0.98 sensitivity, and 0.98 accuracy. The experimental findings concur with expert observations, indicating that the proposed approach is most effective and practical for early diagnosing breast microcalcifications, substantially improving the work efficiency of physicians.