Background: Alternative splicing of the Fas transcript can produce a natural secreted isoform of this molecule. Some cancer cells can also produce soluble Fas (sFas) which may have suppressive effects on the immune system's anti-tumor response. Elevated concentrations of sFas have been detected in the sera of patients with different malignancies.Materials and Methods: The concentrations of sFas in sera of patients with head and neck carcinoma (HNC, n=98) and healthy individuals (n=30) were measured by Sandwich ELISAand compared to values obtained six months after surgical removal of the tumor (n=48). Data were correlated with different clinical findings of the patients.Results: sFas concentrations in the sera of HNC patients were found to be significantly higher in patients with different tumor stages. sFas concentration did not correlate with age or tumor invasiveness, however a higher concentration of sFas was found in the sera of patients who had higher tumor grades. Surgical removal of tumors in patients resulted in a substantial decrease in sFas concentration.Conclusion: The initial rise in sFas concentration in the sera of HNC patients and its consequent decrease could be regarded as a sign of tumor suppressive mechanisms. Additional studies are needed to fully elucidate this mechanism however these findings might show the prospective use of such biomarkers to determine disease prognosis and even immunotherapeutic applications.