The Six Sigma methodology, a data-driven approach to quality management has become a transformative tool in healthcare especially in laboratory diagnostics. This review explores the application of Six Sigma in clinical laboratories, focusing on its potential to enhance diagnostic accuracy, reduce errors and streamline operational efficiency. By minimizing variability and defects in laboratory processes, Six Sigma aims to achieve near-perfect quality, driving improvements in patient outcomes and healthcare delivery. This article delves into the theoretical framework behind Six Sigma, the structured DMAIC process (Define, Measure, Analyze, Improve, Control), and its specific applications in diagnostic laboratories. Additionally, it addresses the challenges faced during implementation and the integration of emerging technologies like AI and automation. Through real-world case studies, the article demonstrates the significant benefits of Six Sigma, such as reduced error rates, faster turnaround times and improved patient safety. Ultimately, this review highlights Six Sigma as a critical tool for advancing diagnostic practices, paving the way for a more efficient and accurate healthcare system.