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AIM: To immunohistochemically examine micrometastasis and VEGF-C expression in hilar bile duct carcinoma (HBDC) and to evaluate the clinical significance of the results. METHODS: A total of 361 regional lymph nodes from 25 patients with node-negative HBDC were immunostained with an antibody against cytokeratins 8 and 18 (CAM 5.2), and immunohistochemical staining of VEGF-C was performed in 34 primary resected tumors. RESULTS: Lymph node micrometastasis was detected in 6 (24%) of the 25 patients and 10 (2.8%) of the 361 lymph nodes. Patients with micrometastasis showed significantly poorer survival rates than those without (P=0.025). VEGF-C expression was positive in 17 (50%) of 34 HBDC, and significantly correlated with lymph node metastasis (P=0.042) and microscopic venous invasion (P=0.035). CONCLUSIONS: It is suggested that immunohistochemically detected lymph node micrometastasis has an impact on the outcome of HBDC. VEGF-C expression is highly correlated with lymph node metastasis in HBDC and might therefore be a useful predictor.