An activating mutation in the activation loop of the EGFR kinase domain, L858R (also identified as Leu834 in a different numbering of the EGFR sequence), is among most frequent mutations in lung cancer, amounting to more than 40% of EGFR mutations in this cancer category, and can result in a dramatic enhancement of EGFR activity [50–52]. The gene discussed is EGFR; the disease is cancer.