Small cell carcinoma (SCC) in the head and neck region is an extremely rare high-grade malignant tumor. The authors report a case of an SCC occurring in the left buccal region. An 85-year-old man exhibited left cheek swelling that rapidly increased in size. Histopathological examination revealed invasive growth of an SCC into the musculo-adipose tissue. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3), neuron-specific enolase (NSE) and CD56, but negative for cytokeratin 20. The patient received chemotherapy and radiotherapy, which resulted in marked regression of the tumor. Surgical resection was performed. The serum levels of NSE and pro-gastrin-releasing peptide (pro-GRP) increased and multiple metastases of the tumor occurred 1 month after surgery. SCCs tend to exhibit aggressive invasion and metastasis so chemotherapy for the whole body is recommended to prevent dissemination of the tumor cells. Serum levels of NSE and pro-GRP are considered to be useful tumor markers for understanding the status of the tumor and the clinical symptoms.