Simple Summary: Lynch syndrome is one of the most common tumor syndromes and the leading cause of hereditary endometrial cancer. International guidelines recommend universal screening for Lynch syndrome in women with endometrial cancer as they may benefit from personalized cancer treatment, targeted cancer surveillance, and risk-reducing prevention strategies. However, testing for Lynch syndrome is not yet well established in clinical practice, compromising optimal medical care for affected women and their at-risk relatives. In this study, we examine the implementation of Lynch syndrome screening using real-world data. We further analyze intermediate steps of testing for common sources of error and investigate patient risk factors leading to non-adherence to testing. To promote precision healthcare and ensure future quality of care for Lynch syndrome patients, we discuss strategies to optimize the Lynch syndrome screening algorithm in clinical practice. Lynch syndrome is an inherited tumor syndrome caused by a pathogenic germline variant in DNA mismatch repair genes. As the leading cause of hereditary endometrial cancer, international guidelines recommend universal screening in women with endometrial cancer. However, testing for Lynch syndrome is not yet well established in clinical practice. The aim of this study was to evaluate adherence to our Lynch syndrome screening algorithm. A retrospective, single-center cohort study was conducted of all endometrial cancer patients undergoing surgical treatment at the Bern University Hospital, Switzerland, between 2017 and 2022. Adherence to immunohistochemical analysis of mismatch repair status, and, if indicated, to MLH1 promoter hypermethylation and to genetic counseling and testing was assessed. Of all 331 endometrial cancer patients, 102 (30.8%) were mismatch repair-deficient and 3 (0.9%) patients were diagnosed with Lynch syndrome. Overall screening adherence was 78.2%, with a notable improvement over the six years from 61.4% to 90.6%. A major reason for non-adherence was lack of provider recommendation for testing, with advanced patient age as a potential patient risk factor. Simplification of the algorithm through standardized reflex screening was recommended to provide optimal medical care for those affected and to allow for cascading testing of at-risk relatives. [ABSTRACT FROM AUTHOR]