According to the 2005 World Health Organization classification of head and neck tumors, neuroendocrine tumors can be subdivided into typical carcinoid, atypical carcinoid, and small cell carcinoma. Similar tumors diagnosed as large cell neuroendocrine carcinomas (LCNECs) in the lung are diagnosed as atypical carcinoids in the head and neck region. We studied neuroendocrine tumors and analyzed whether LCNEC should be separated from atypical carcinoid in the head and neck region. Twenty-three cases of primary head and neck neuroendocrine tumors were included and subdivided into typical carcinoid, atypical carcinoid, and small cell carcinoma according to the 2005 World Health Organization guidelines, and then LCNECs were separated from atypical carcinoids according to modified criteria using the Ki-67–labeling index and mitotic count. Clinical information and survival data were obtained, and immunohistochemical studies for p53 were conducted. The 5-year survival rates for the 2 typical carcinoids, 7 atypical carcinoids, 7 LCNECs, and 7 small cell carcinomas were 100.0%, 83.3%, 21.4%, and 20.8%, respectively (P=0.032). The LCNEC patients were older (mean age, 61 vs. 41 y; P=0.038), more commonly in advanced stage (stages III and IV 100% vs. 28.6%, P=0.01), with a poorer prognosis (5-year survival 21.4% vs. 83.3%, P=0.03), and more commonly had tumors overexpressing p53 (85.7% vs. 0%, P=0.005) as compared with atypical carcinoid patients. LCNECs should be separated from atypical carcinoids as a new entity of neuroendocrine carcinoma in the head and neck region. The new classification may provide better risk stratification and useful information for proper treatment.