To study the therapeutic outcome of patients with extensive small-cell lung cancer (SCLC) with the brain as the single site of metastases at initial diagnosis, we retrospectively reviewed the outcome of 30 such patients (23 men and seven women; median age, 59 years; range, 36-74 years). Medical histories were taken, and physical examination, complete blood cell count, chemistry profile, chest radiography, radionuclide bone scan, computed tomography (CT) scan of the abdomen or radionuclide liver scan, and CT scan of the head were performed as the staging workup for each patient. Bone marrow biopsies were performed in 19 patients. All patients initially received cisplatin-based chemotherapy and concomitant whole-brain radiation therapy consisting of 3,600-4,800 cGy. Subsequently, 22 patients also received thoracic radiation therapy (17 patients as part of the protocol treatment and five patients at the time of disease progression). Thirteen patients had a complete response, 11 had a partial response, three had regression, and three had stable disease. Median survival of the entire group was 14 months (range, 1.4-70.7 months). Twenty-four patients eventually had progression of disease, with a median time to progression of 10 months (range, 2.3-48.5 months). Only one patient had disease progression in the brain (12.6 months after diagnosis). Twenty-two patients eventually died of the disease. The results of our study suggest that the therapeutic outcome in SCLC with the brain as the single site of metastases at initial diagnosis is similar to that of limited-stage SCLC.