Background: Breast cancer remains a significant public health concern, and the early detection of the disease is crucial for improving patient outcomes. This prospective, comparative study aimed to meticulously evaluate and compare the accuracy of mammography and ultrasound in detecting breast cancer, focusing on their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Methods: A total of 250 women aged 40 to 75 years, presenting for routine screening or with symptomatic breast complaints, were included in the study. Participants underwent digital mammography and high-resolution ultrasound examinations, with the findings classified according to the Breast Imaging Reporting and Data System (BI-RADS). Biopsy-confirmed results served as the reference standard.Results: Of the 250 participants, 36 (14.4%) were found to have biopsyconfirmed breast cancer. Ultrasound demonstrated a higher sensitivity of 94.4% (95% CI: 80.8%-99.3%) compared to mammography at 83.3% (95% CI: 67.2%-93.6%), with a statistically significant difference in detection rates (p = 0.031). The combined use of both modalities achieved the highest sensitivity of 97.2% (95% CI: 85.5%-99.9%). The specificity was 89.4% for mammography and 87.0% for ultrasound, with a modest decrease to 86.4% for the combined approach. The PPV ranged from 57.4% to 60.0%, while the NPV was exceptionally high, reaching 99.5% for the combined modalities.Conclusion: Ultrasound demonstrated superior sensitivity compared to mammography in detecting breast cancer, particularly in women with dense breasts. The combined use of both modalities resulted in the highest sensitivity, suggesting that a multimodal approach may be the most effective strategy for comprehensive breast cancer screening and diagnosis.