Background Contrast-enhanced spectral mammography (CESM) is a relatively newly developed advanced application with modification of digital mammography by the use of a contrast agent, but still has little known efficacy among Egyptian patients. Our aim in this study is to share our initial experience in evaluating symptomatic patients with different ACR breast parenchyma especially in dense breast parenchyma as it is always challenging in diagnosis. Results CESM in this study gave a sensitivity of 92% and specificity of 85% in characterization of benign and malignant lesions. For postoperative cases, sensitivity was 85% and specificity was 60%. For chemotherapy cases, sensitivity was 85% and specificity was 76%. Contrast uptake was noted in 68% of masses. Cavitary benign lesions were noted in 22.1% of cases. Multifocal and multicentric carcinomas were detected in 39.7% of pathologically proved malignant masses. Statistical analysis revealed sensitivity, specificity, and accuracy of 82.9%, 76.5%, and 81.0% for conventional mammograms as compared to 92.7%, 82.4%, and 89.7% for CESM respectively. Conclusion CESM is a promising technique that can enhance the specificity of conventional mammograms. It is an easy, simple, and rapid contrast-based procedure, especially for characterization of lesions in dense breast parenchyma. It performs proper diagnosis for high-risk patients and follow-up response to different lines of management.