Tumor sequencing showed a high mutational burden...Immunohistochemical staining was negative for PD-L1 expression. Our case demonstrated a partial response and a long-term remission from the front-line single-agent pembrolizumab in a woman with metastatic uterine serous carcinoma and Lynch syndrome due to a germline MSH6 gene mutation...Our experience suggests a potential significant clinical benefit of checkpoint inhibitors used as single agents early on in the treatment of MMR-deficient/MSI-H/hypermutated uterine cancers...