The cancer-predisposition syndrome, Lynch syndrome, is caused by pathogenic germline variants in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 ̧ or PMS2. Beside a high risk of colorectal and endometrial cancer, Lynch syndrome has been linked to an increased risk of both upper (ureteral and renal pelvic) and lower (bladder) urothelial cancer (1–4), with urothelial cancers being the third most common cancer in this population. Here, MSH6 is linked to cancer.