The purpose of this study was to investigate the association of the expression of vascular endothelial growth factor-C (VEGF-C) with regional lymph node metastasis in oral squamous cell carcinoma (OSCC). The expression of VEGF-C in biopsy specimens obtained from 62 patients with OSCC was examined by immunohistochemistry. In the early stages of T1 and T2 (38 cases), VEGF-C expression strongly correlated with lymph node metastasis (P<0.001), and the percentage of VEGF-C-positive staining was 88.2% for patients with lymph node metastasis (15 of 17 cases) and 28.6% for those without lymph node metastasis (6 of 21 cases). However. in the advanced stages of T3 and T4, no significant correlation between VEGF-C expression and lymph node metastasis was observed. These results indicate that VEGF-C expression in biopsy specimens can be used as a reliable predictor of regional lymph node metastasis, particularly in early OSCC, and may become an important factor in the selection of appropriate treatment. (C) 2003 Elsevier Science Ltd. All rights reserved.