Background <p>This systematic review investigated the diagnostic performance and emerging applications of ultrasonography in the early detection of breast cancer between 2015 and 2025. Early detection is crucial in reducing breast cancer morbidity and mortality, particularly among women with dense breast tissue or in low-resource settings where traditional screening tools like mammography are limited. Despite widespread usage, there is significant variation in the reported diagnostic accuracy of ultrasonography, largely due to differences in imaging protocols, operator expertise, and technological enhancements.</p> Methods and Results <p>This review synthesizes findings from 17 studies encompassing over 30,000 women across high- and low-income countries, reporting pooled sensitivity and specificity rates ranging from 85% to 100% and above 85%, respectively. Advanced techniques, including contrast-enhanced ultrasound and artificial intelligence-assisted models, have further improved lesion characterization and reduced interpretation variability. The results indicate that ultrasonography, especially when augmented with AI and standardized protocols, can serve as an effective first-line or supplementary tool for early breast cancer screening. However, operator dependency, lack of universal imaging standards, and inconsistent access remain significant challenges.</p> Conclusion <p>The findings of this review highlight the need for broader integration of portable ultrasound and AI-driven diagnostics, particularly in underserved settings. Implementing the targeted training programs, harmonized imaging protocols, and research into predictive ultrasound technologies will be critical in maximizing its diagnostic potential and reducing global disparities in breast cancer outcomes.</p>