We report two cases of central nervous system metastases from non-small cell lung cancer in patients being administered gefitinib, which improved after changing treatment to erlotinib. Case 1: A 57-year-old man developed carcinomatous meningitis while receiving third-line treatment with gefitinib after surgery for lung cancer. His symptoms markedly improved upon changing treatment to erlotinib. Case 2: A 54-year-old woman developed multiple brain metastases during third-line treatment with gefitinib. After changing her treatment to erlotinib, enhanced head MRI showed that the size of brain lesions had decreased. At the recommended dosage, erlotinib showed higher blood concentrations than gefitinib, and may also have been higher in cerebral spinal fluid. This may explain the difference in efficacy between gefitinib and erlotinib in central nervous system metastases.