Squamous cell carcinoma (SCC) antigen is a tumor-associated antigen isolated from the squamous cell carcinoma of the uterine cervix. In order to estimate the usefulness of the SCC antigen in monitoring the clinical behaviors of oral squamous cell carcinomas, we analyzed clinicopathologically and immunohistochemically 54 cases of squamous cell carcinoma of the oral cavity. Elevated serum SCC antigen levels were detected in 23 (42.6%) out of 54 oral squamous cell carcinomas. The positive rate of serum SCC antigen levels was significantly higher in the patients with advanced clinical stages and poorly differentiated carcinoma. The serum levels declined rapidly after the surgical operation. It is considered that the serum SCC antigen levels could be useful in monitoring the extension, effectiveness of therapy, recurrence and metastases of the oral squamous cell carcinomas. Immunohistochemically, strong staining was seen in the cytoplasm of the well-differentiated carcinoma cells.