PURPOSE: Understanding the genetic heterogeneity of Lynch syndrome (LS) cancers has led to significant scientific advancements. However, these findings are widely dispersed across various resources, making it difficult for clinicians and researchers to stay informed. Furthermore, the uneven quality of studies and the lack of effective translation of knowledge into clinical practice create challenges in delivering optimal patient care. To address these issues, we developed and launched the Precision Lynch Syndrome Knowledge Base (PLSKB), a specialized, interactive web-based platform that consolidates comprehensive information on LS. METHODS: To create the PLSKB, we conducted an extensive literature review and gathered data from reliable sources. Through an extensive literature review and survey of other reliable sources, we have extracted prominent and relevant content with a high level of accuracy, transparency, and detailed provenance. To enhance usability, we implemented an evidence-leveling framework, categorizing studies on the basis of the type of research, reliability, and applicability to clinical care. The platform is designed to be dynamic, with updates performed monthly to incorporate the latest research. RESULTS: The PLSKB integrates a broad spectrum of data related to LS, including biomarkers, cancer types, screening and prevention strategies, diagnostic methods, and therapeutics options. This centralized resource is intended to support clinicians and researchers in making evidence-based decisions throughout surveillance and care processes. Its interactive design and frequent updates ensure that users have access to the most current and relevant findings. CONCLUSION: The PLSKB bridges the gap between research and clinical practice by offering a reliable, up-to-date repository of evidence-based information. This tool empowers clinicians and researchers to deliver precision care and advance research for LS and related conditions, ultimately improving patient outcomes.