Although failure of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) is generally believed to be associated with cross-resistance to other EGFR TKI, the benefit of administering erlotinib as a second EGFR TKI after resistance of gefitinib as the first TKI has been well known. However, good response to gefitinib after an initial response to erlotinib has been rare. We report that a 45-year-old woman (never smoked), with lung adenocarcinoma and EGFR mutation, showed an initial response to erlotinib, and then responded to gefitinib again.