Emerging evidence suggests that the T790M ‘gatekeeper’ mutation may exist in lung tumours before EGFR-TKI therapeutic selection (Bell et al, 2005; Godin-Heymann et al, 2007), partly due to its enhanced oncogenicity, and accounts for the adverse clinical course and outcome in gefitinib/erlotinib-resistance lung cancers after a course of rapid TKI selection. The gene discussed is EGFR; the disease is lung cancer.