To review the biologic behavior, therapy and natural courses of patients with extrapulmonary small cell carcinoma (EPSCC) in a medical center.We used the computer assisted search for patients diagnosed with EPSCC registered from July 1986 through April 2005. The eligible patients had pathologically proven SCC in sites other than the lung and normal chest radiographs, computed tomography of the chest, sputum cytology, and/or negative bronchoscopic findings.Twenty patients with EPSCC were identified and 12 patients (60%) had limited disease (LD). For the patients with LD receiving systemic chemotherapy, the response rate was 73% (36.5% complete response (CR), 36.5% partial response (PR). However, most of the patients experienced rapid systemic recurrence, with a median disease free survival (DFS) of 8 months. Patients with extensive disease (ED) received mostly etoposide-cisplatin (EP) based chemotherapy, for which the response rate was 50%. The median overall survival (OS) of the patients with LD and ED was 22 months and 3 months. The patients with EPSCC of the head and neck region showed a favorable clinical course, with a median OS of 43 months. Patients with EPSCC of sites other than the head and neck region had aggressive courses with a median OS of 15.5 months.Integrated chemoradiotherapy with surgery for patients with LD generates realistic survival results. EP-based chemotherapy should be the current chemotherapy regimen of choice for patients with ED. Patients with EPSCC of sites other than the head and neck region was usually had poor overall outcomes.