Objective: To investigate the expression of vascular endothelial growth factor C (VEGF-C) and its receptor Flt-4 in human tongue squamous cell carcinomas (TSCC) to elucidate their role in lymph node metastasis and other clinical significance. Methods: The expression of VEGF-C and Flt-4 was examined in 22 fresh biopsy specimens by RT-PCR and 55 surgical specimens of human TSCC by immunohistochemistry. Results: VEGF-C mRNA was detected in 16 (72.7%) of 22 fresh specimens, which was higher than that in the normal mucosa. In the 16 VEGF-C mRNA positive cases, 12 Flt-4 mRNA were positive, a significant relationship between VEGF-C and Flt-4 mRNA expression. In the 55 surgical specimens of TSCC, 29 (52.7%) showed VEGF-C positive in the cytoplasm of tumor cells. Flt-4 was mainly expressed in the lymphatic endothelial cells. Normal tissue exhibited no or faint VEGF-C. VEGF-C expression correlated with grade of tumor pathology and lymph node metastasis. Conclusion: The results overall suggest that VEGF-C/Flt-4 may play an important role in the lymph node metastasis and it could be a useful biological marker to foresee the cervical lymph node metastasis and prognosis.