Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinases, and shows favorable antitumor activity against chemorefractory non-small cell lung cancer (NSCLC). The majority of responders (patients who are sensitive to gefitinib), however, relapse within 1.5 years, indicating an acquired resistance to gefitinib. Here we report three chemotherapy refractory NSCLC patients who were retreated with gefitinib. All three cases were nonsmokers and showed an adenocarcinoma histology. While they had experienced successful control from their initial treatment with gefitinib for more than 12 months, gefitinib therapy was terminated because two cases (cases 1 and 3) relapsed during the therapy and case 2 suffered alveolar hemorrhage. After more than 7 months from the time of discontinuation of the initial gefitinib treatment, they were retreated with gefitinib, as further tumor progression was observed. Of the three cases, cases 1 and 2 were well controlled by retreatment with gefitinib monotherapy for more than 7 months, suggesting sensitivity to retreatment. Case 3 also showed a regression in size of several tumors, while some other lesions progressively enlarged and developed a malignant pleural effusion after 4 months. These observations suggest the possibility that retreatment with gefitinib might be useful when 1) initial treatment shows a favorable clinical response, and 2) there has been a period of time following the termination of the initial gefitinib treatment.