Objective: We retrospectively analyzed the effectiveness of Gamma Knife surgery (GKS) for metastatic brain tumors from lung cancer without prophylactic whole brain radiation therapy. Methods: Six hundred eight consecutive patients who satisfied the following 5 criteria were analyzed: (1) lung cancer primary; (2) no surgically inaccessible lesions; (3) tumor number and size limited to 10 J of total skull internal dose; (4) no symptomatic carcinomatous meningitis; (5) Karnofsky performance status score no lower than 70 due to systemic disease. Large tumors were totally removed, while smaller lesions were all irradiated with GKS. New lesions detected with follow-up magnetic resonance imaging were appropriately re-treated with GKS. Overall survival (OS), neurological survival (NS), qualitative survival (QS) and new lesion-free survival curves were calculated and the prognostic values of covariates were obtained. Results: In total, 1,101 separate sessions were required to treat 6,427 lesions. This series includes 68 small cell cancers and 80 craniotomies. The median OS period was 10.4 months. In multi-variate analysis, significant prognostic factors for OS were extracranial disease (risk factor: active), Karnofsky performance status score (< 70) and gender (male). NS and QS at I year were 88.0 and 81.3%, respectively. The only significant poor prognostic factor for NS was carcinomatous meningitis. Male gender, active extracranial disease, low Karnofsky performance status score, magnetic resonance imaging evidence of carcinomatous meningitis and a large total tumor volume were significant factors influencing QS. New lesion-free survival at 6 months was 71.5%. The treatment cost of this protocol was estimated USD 9,000 per patient, which is nearly the same as that of GKS with upfront whole brain radiation therapy. Conclusion: In terms of NS and QS, GKS alone for metastatic brain tumors from lung cancer provides excellent palliation without prophylactic whole brain radiation therapy. Close observation and appropriate salvage treatment are essential for prevention of neurological death and maintaining of activities of daily living. Copyright (c) 2006 S. Karger AG, Basel.