As the maintenance medium of the oral cavity, saliva is secreted from exocrine glands that include the parotid, submandibular, sublingual, and minor salivary glands. Considering that saliva is a fluid suffused with protein, it is possible that the solubilized by-products of oncogenic expression may be present in saliva. Recent studies suggest the presence of solubilized extracellular domain portion of the c-erbB-2 protein in serum, nipple aspirates, and saliva. As a consequence, the purpose of this study was to determine the presence and concentration of c-erbB-2 in major salivary gland secretions. Fifteen healthy women had serum, stimulated whole (SWS), parotid (SP), and submandibular/sublingual (SS) salivary secretions collected. The specimens were analyzed for c-erbB-2 using enzyme linked immunosorbent assays (ELISAs). Western blots using c-erbB-2 were also performed on these specimens. The ELISAs revealed the presence of c-erbB-2 in SWS (24.50 Units/ml), SP (19.66 Units/ml), SS (15.59 Units/ml) and serum (1472.15 Units/ml). Western blots confirmed the presence of these 185 kDa proteins. These results suggest that the protein, c-erbB-2, is present in relatively equal amounts in both SP and SS glandular secretions. Elevated glandular salivary c-erbB-2 concentrations could be useful as a preliminary, non-invasive test in clinical decision making when diagnosing salivary gland carcinomas. Additionally, this marker may have utility in distinguishing between oral lesions that are benign, pre-malignant and malignant in the oral cavity. Further research is required to determine if these findings have clinical utility.