Vascular endothelial growth factor C (VEGF-C), a member of VEGF gene family, is considered to induce both lymph node metastasis and lymphatic involvement in various cancers related to lymphangiogenesis. We examined the relationship between VEGF-C expression and clinicopathological features in 112 Japanese patients with esophageal squamous cell carcinoma (ESCC) who underwent esophagectomy and reconstruction without preoperative treatment. VEGF-C expression was examined using immunohistochemical staining and RT-PCR in surgically resected tissues. Regarding VEGF-C there were positive findings in 44 (39.3%) cases. VEGF-C expression in ESCC significantly correlated with the depth of tumor (p=0.0131), lymph node metastasis (p=0.0211), lymphatic involvement (p<0.0001) and pathological stage (p=0.0164). The prognosis for the VEGF-C positive group was poorer than that for the VEGF-C negative group (p=0.038). Multivariate analysis indicated that VEGF-C expression in ESCC is an independent factor only in cases of lymphatic involvement. VEGF-C expression in ESCC may play a great key role in lymphatic spread and this may be a consideration in terms of deciding the most appropriate treatment.