Biological resistance to both EGFR- and HER2-targeted therapies, due to mutations in for example PI3K/AKT, Ras/Raf/Mek/Erk or other intracellular signal pathways has been observed for many types of cancer.1–4 Urinary bladder cancer is at present not generally considered for therapy with EGFR-or HER2-binding agents such as tyrosine kinase inhibitors and “naked” antibodies (e.g. trastuzumab or cetuximab). The gene discussed is ERBB2; the disease is urinary bladder cancer.