We describe the prevalence of pathogenic/likely pathogenic germline variants in patients with UTUC and bladder cancer, and characterize the personal and family cancer histories of patients with MMR (<i>MSH2</i>, <i>MSH6</i>, <i>MLH1</i>, and <i>PMS2)</i> and HRR (<i>BRCA1</i> and <i>BRCA2,</i> among others) variants, comparing with an institutional cohort of MMR carriers (<i>n</i> = 35; 2012-2025). This evidence concerns the gene MSH2 and renal pelvis/ureter urothelial carcinoma.