Evidence from lung cancer (Engelman et al, 2007), pancreatic cancer (Frolov et al, 2007), melanoma (Reschke et al, 2008) and head and neck cancer (Erjala et al, 2006) suggest that ErbB3-dependent signalling mechanisms are important for not only disease progression, but also resistance to EGFR-targeted therapies. The gene discussed is EGFR; the disease is head and neck cancer.