Drs. Mantia and Berg discuss HER2 as a biomarker in genitourinary cancers, focusing on testing strategies, prevalence, and the clinical implications of HER2 expression and ERBB2 mutations for patient management. They also review new data from ESMO 2025, highlighting the DISTINCT-1 trial and a HER2-targeted approach for high-risk upper tract genitourinary carcinoma.