Recent genomic analyses of UTUC2–5 have identified a high incidence of potentially actionable genomic alterations including recurrent activating mutations in receptor tyrosine kinases (FGFR3, ERBB2), HRAS, PIK3CA and TSC1. These molecular profiling studies have also, however, identified significant genetic diversity among UTUC patients and a large number of genomic variants of unknown significance6,7. The gene discussed is ERBB2; the disease is renal pelvis/ureter urothelial carcinoma.