Objectives: This study was designed to investigate the significance of serum SCC antigen, CA 19-9, CA 125 level and DNA microsatellite alterations (MSA) as prognostic factors and indicators for recurrences in the pre-treatment and post-treatment state, respectively in head and neck cancer patients. Materials and Methods: 120 patients who received curative treatment for head and neck cancer from 1995 to 2000 were followed up successfully, and were analyzed retrospectively. Thirty healthy subjects served as normal controls. Serum SCC Ag levels were measured by microparticle enzyme immunoassay technique via IMX SCC assay, CA 19-9 levels were measured by CA 19-9 RIA test kit, and CA 125 levels were measured by CA 125 IRMA kit. MSA were identified after PCR amplification. Heterozygosity was considered lost if the ratio of one allele was significantly decreased (>50%) in serum DNA compared with normal DNA from lymphocytes. Results: Preoperative tumor markers were higher in cancer patients than control, but not significant. Postoperative SCC Ag levels were lower than preoperative levels. The SCC Ag levels were remained low in no evidence of disease (NED) group, but increased in locoregional recurrence and distant metastasis group. CA 19-9 and CA 125 levels showed no correlation between levels and recurrences and were not decreased significantly after primary tumor removal. MSA were detected in five out of 21 cases, and highly detected in distant metastasis group. Conclusion: SCC Ag seems to be a helpful serum tumor marker for early detection of recurrence and distant metastasis of head and neck cancer after curative treatment. But, CA 19-9 and CA 125 were not reliable markers for head and neck tumors. MSA were not statistically significant because of the small number of study group. However they may be helpful for screening serum molecular markers for early detection of distant metastasis of head and neck cancers.