The efficacy of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib is difficult to be accurately assessed in patients with non-small cell lung cancer (NSCLC) because it is commonly employed after failure of another EGFR-TKI, gefitinib.Medical records from 104 patients with NSCLC treated with erlotinib were retrospectively reviewed.There were no significant differences in erlotinib efficacy between EGFR-mutated NSCLC with gefitinib resistance and NSCLC with wild-type EGFR. A therapeutic response of disease control (DC) and the onset of skin rash prolonged the progression-free survival (PFS), whereas the onset of interstitial lung disease shortened both PFS and overall survival (OS). The DC group also experienced prolonged OS.Erlotinib may be a therapeutic option for EGFR-mutated NSCLC with gefitinib resistance, as well as for NSCLC with wild-type EGFR. Therapeutic response of DC and the onset of the described adverse events may be practical predictors of survival in erlotinib treatment.