ERBB2 encodes HER2, a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. ERBB2 mutations have been reported in ~12% of urothelial carcinomas. This particular variant I767M lies within the protein kinase domain of HER2 and has been shown to result in increased kinase activity in vitro. This variant has been identified in rare cases of urothelial carcinomas, among other cancer types, and is considered to be oncogenic. Further studies are needed to elucidate the role of anti-HER2 therapy in this setting. Clinical correlation is recommended.