Two patients with non-small cell lung cancer presented with multiple brain metastases. They received gefitinib orally for the treatment of the primary lung lesions. About one month later, the brain metastases unexpectedly disappeared or became smaller. The patients survived without recurrence of brain metastases and growth of lung lesions for 3-4 years. Gefitinib is a selective epidermal growth factor receptor tyrosine kinase inhibitor and is approved for use in the treatment of non-small cell lung cancer. Gefitinib may be very effective for multiple brain metastases in patients with non-small cell lung cancer.