Gefitinib is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and it shows favorable antitumor activity against chemorefractory non-small cell lung cancer (NSCLC), especially with EGFR gene mutations. On the other hand, patients with NSCLC have few treatment options available if they acquire resistance to gefitinib or severe adverse events occur. We report a 73-year-old small woman diagnosed with NSCLC who was treated with gefitinib (250 mg/day) every other day or by 7-days-on followed by 7-days-off therapy dose schedule after severe paronychia appeared. The best response was stable disease (SD), which lasted 9 months. Dose reescalation of gefitinib to 250 mg/day was chosen after progression of disease was demonstrated. Most lesions decreased in size again and this lasted for more than 5 months. EGFR gene analysis showed point mutation of codon 861 in exon21 (L861Q). On the other hand, T790M was not detected. These observations suggest the possibility that treatment with dose-escalated gefitinib might be useful even after resistance to initial dose of gefitinib is acquired if initial treatment shows a favorable clinical response.