1575 Background: Although chemotherapy has not yet emerged as a standard therapy for patients with brain metastasis, evidences suggest that chemotherapy may have a role in the treatment of selected patients. Methods: We have evaluated 63 consecutive non-small cell lung cancer (NSCLC) patients with synchronous brain metastasis (BM) who had not been previously treated. After cranial radiation therapy (RT), all patients in ‘the chemotherapy arm’ (CTX) were treated with platinum-based combination chemotherapy, and best supportive care was selected for patients in ‘the no-chemotherapy arm’ (no-CTX). Results: The median age of all patients was 55 years. The performance status of all patients was ECOG grade 1–2. Thirty-one of the 63 patients received systemic chemotherapy. In the CTX arm, a paclitaxel + platinum (cisplatin or carboplatin) chemotherapy was administered in 38.7%, gemcitabine + platinum in 25.8%, and vinorelbine + platinum in 25.8% as the first-line chemotherapy. Seventeen patients were treated with a second-line chemotherapy, and 8 patients of them received paclitaxel + platinum followed by gemcitabine + platinum or vice versa. Extracranial overall responses were 36% in the first-line chemotherapy and 35% in the second-line, and the median response durations were 29.1 weeks and 30.4 weeks, respectively. The pattern of treatment failure revealed that ‘progression of the extracranial lesion’ (58.1%) was occurred more frequently than the ‘aggravation of neurologic status’ (19.4%) in the first-line chemotherapy. The causes of failure were identical in the second-line chemotherapy. The median overall survival of the CTX arm is significantly longer than that of the no-CTX arm (58.1 weeks vs. 19.0 weeks, p<0.001). Toxicity in the CTX arm was tolerable. Conclusions: The systemic chemotherapy was effective in increasing the overall survival of patients with BM from NSCLC, and extracranial progression was the main cause of chemotherapeutic failure. No significant financial relationships to disclose.