OBJECTIVE To examine the expression of vascular endothelial growth factor C (VEGF-C) in human esophageal squamous cell carcinoma (ESCC), and to clarify its role in lymphatic metastasis in ESCC patients. METHODS Esophageal carcinoma EC9706 cells and samples from 49 patients with primary ESCC were investigated by using S-P immunohistochemistry (IHC), the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) methods for VEGF-C expression.RESULTS VEGF-C positive expression was found in EC9706 cells through IHC, ISH and RT-PCR. Positive IHC for VEGF-C was observed in 36 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in a lymph-node-positive group compared to a node-negative group (χ2=4.7, P＜0.05). Positive ISH for VEGF-C mRNA was observed in 23 of 49 cases of ESCC. There was a significant difference between the expression of VEGF-C in the lymph-node-positive group and node-negative group (χ2=31.3, P＜0.01). The expression of VEGF-C was significantly higher in the lymph-node-positive group compared to the node-negative group. Of 49 ESCC tissues, RT-PCR for VEGF-C mRNA was observed positively in 29 cases. There was a significant difference between the expression of VEGF-C in the lymphnode-positive group and node-negative group (χ2=23.3, P＜0.01). The expression of VEGF-C was significantly higher in the lymph node-positive group compared to the node-negative group. Expressions of VEGF-C were not significantly associated with age, gender, and pathological grade. There was a relationship between VEGF-C mRNA expressions by RT-PCR and ISH (χ2=18.5, P＜0.01) in ESCC cases, but with no significant difference between the two methods.CONCLUSION VEGF-C expression may induce lymphangiogenesis in human ESCC. There was a close correlation between VEGF-C expression and lymph node metastasis. VEGF-C can serve as a useful prognostic factor for ESCC patients.