Oncogenic addiction to other altered signaling pathways, including human epidermal growth factor receptor 2 (HER2)- and mammalian target of rapamycin (mTOR), is not uncommon in UTUC, with ERBB2-activating mutations and/or amplifications detectable in 8% of cases and TSC1/TSC2-truncating mutations and/or deletions in up to 18% (Figure 1). This evidence concerns the gene MTOR and renal pelvis/ureter urothelial carcinoma.