EGFR mutations have been reported in up to 5% of gastric cancers. The prognostic and predictive implications of EGFR mutations in gastric cancer have not been fully determined. Multiple clinical trials involving EGFR small molecule inhibitors and monoclonal antibodies are present, but limited and conflicting data preclude the therapeutic significance of EGFR mutations in gastric cancer. In NSCLC, an acquired T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. Third generation TKIs (e.g. osimertinib) have been shown to be effective in lung adenocarcinomas with the EGFR T790M mutation. A germline EGFR T790M mutation results in a rare lung cancer hereditary syndrome associated with increased risk in never-smokers. The presence of a germline EGFR T790M mutation also predicts for resistance to standard TKIs. The significance of EGFR T790M in gastric cancer should be considered in a relevant clinical context.