Monoclonal antibody 17.13.Cl.10 is a murine IgM kappa monoclonal antibody (Mab) that stains frozen section squamous cell carcinoma (SCC) homogeneously and intensely with a sensitivity greater than 98%, including 106/107 SCC specimens from the head and neck. It was produced using a human laryngeal SCC as immunogen and screened using frozen section human tissue. Monoclonal antibody 17.13.Cl.10 faintly stains the basal layer of normal squamous epithelium, does not stain normal organ tissue other than myoepithelial cells, and reacts with few non-SCC tumors. It, therefore, may be a useful adjunct to standard histopathologic criteria for the diagnosis of SCC. It may prove helpful in the investigation of tumor-associated antigens. Despite major technical and immunologic problems, monoclonal antibodies to functional tissue-specific tumor-associated antigens have the potential to play a major role in imaging and in treatment in the future.