Head and neck squamous cell carcinomas (HNSCC) are characterized by a marked propensity for local invasion and cervical lymph node metastasis. The aim of this study was to investigate the expression of epidermal growth factor receptor (EGFR), c-erbB-2, vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in tumor samples of 91 HNSCC patients, and to study a possible correlation to various clinico-pathologic parameters. The expression of EGFR, c-erbB-2, VEGF, MMP-2, -3 and -9 was analyzed in the same paraffin embedded tissue by semi-quantitative immunohistochemical staining. High expression of EGFR, c-erbB-2, MMP-2 or -9 was associated with advanced clinical stages, nodal metastases and tumor-stages. However, high expression of VEGF or MMP-3 was not associated with any clinico-pathologic parameters except significant correlation between VEGF and the tumor site. There were significant correlations between EGFR, c-erbB-2, MMP-2 and -9 in HNSCC patients. Conversely, no correlation was found between VEGF or MMP-3 and the other markers. However, significant correlation was found between MMP-3 or -9 and VEGF. The results indicate that the expression of EGFR, c-erbB-2, VEGF or MMPs play an important role in tumor growth, invasion and metastasis in HNSCC. The authors conclude that EGFR, c-erbB-2, MMP-2 and -9 could be good independent prognostic markers, but not VEGF and MMP-3.