Objective To elucidate the effects of vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR-3), in malignant melanoma lymphangiogenesis and lymphatic metastasis, we observed the expression of VEGF-C and VEGFR-3 in proteins and mRNA level in malignant melanoma. Methods The expression of VEGF-C and VEGFR-3 protein was examined in 48 human malignant melanoma cases (30 paraffin-embedded specimens and 18 fresh tumor specimens) by immunohistochemistry and VEGF-C and VEGFR-3 mRNA was examined in 18 fresh tumor specimens using RT-PCR. lymphatic vessel endothelial hyaluronic acid receptor(LYVE-1) was measured for detecting lymphatic vessels, and lymphatic vessel density (LMVD) was observed in lymph node metastatic and non-metastatic malignant melanoma. Results VEGF-C and VEGFR-3 proteins were detected in malignant melanoma cells, vascular endothelium and lymphatic endothelium in peritumor stroma also showed VEGFR-3 expression. The expression of VEGF-C and VEGFR-3 protein in lymph node metastatic malignant melanoma was significantly higher than that in the non-metastatic group respectively (P<0.05). Eighteen fresh tissue samples were examined for gene expression of VEGF-C and VEGFR-3 using RT-PCR, the VEGF-C and VEGFR-3 mRNA levels were significantly higher in the lymph node metastatic group than that in the nonmetastatic group, respectively (P<0.01). LYVE-1 was mainly expressed mainly in the lymphatic endothelium in peritumor stroma, LMVD was 9.845±2.454 and 6.534±2.193 in the metastatic and non-metastatic group, respectively, and the LMVD was significantly higher in the lymph node metastatic group than that in the non-metastatic group (P<0.01). Conclusion Higher expression of VEGF-C in malignant melanoma can up-regulate the expression of VEGFR-3, and the interaction of VEGF-C and VEGFR-3 can facilitate tumor lymphangiogenesis and lymph node metastasis in malignan