Serum biomarkers could be helpful to characterize head and neck squamous cell carcinoma (HNSCC). Thus, the purpose of this systematic review and meta-analysis was to determine the diagnostic capability of serum biomarkers in the assessment of HNSCC patients. Studies were gathered by searching LILACS, PubMed, Science Direct, Scopus and Web of Science up to April 10th, 2015. Studies that focused on serum biomarkers in the diagnosis of HNSCC compared with controls were considered. Sixty-five studies were identified, and the sample size included 9098 subjects. Combined biomarkers demonstrated improved accuracy than those tested individually. Therefore, 12.8% of single and 34.3% of combined indicated that serum biomarkers discriminate patients with HNSCC from controls. The combined biomarkers with better diagnostic capability included Epidermal growth factor receptor (EGFR) + Cyclin D1 and squamous cell cancer-associated antigen (SCCA) + EGFR + Cyclin D1. Beta(2)-microglobin may also be a promising single biomarker for future studies. Serum biomarkers can be potentially useful in the diagnosis of HNSCC. However, further research is required to validate these biomarkers Ver menos