Lynch syndrome, driven by pathogenic variants in MMR genes like MSH2, significantly increases the risk of colorectal and extracolonic cancers. Variants of uncertain significance (VUS) complicate clinical decision-making, as they are not considered actionable. This case highlights the importance of periodic VUS re-evaluation using updated evidence, such as tumorIHC, functional assays, and familial segregation. This enabled reclassification of a VUS to VUSD with probable damaging effect (VUSD), guiding more personalized risk management and screening strategies.