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Background: Liver metastasis (LM) is the determining factor of poor prognosis in colorectal cancer (CRC). Peripheral lymphatico-venous communications have been discussed as a potential pathway of tumor cell dissemination for the development of LMs. In the current study, we investigated the clinical impact of the lymphangiogenic activity in CRCs and their corresponding LMs., Patients and Methods: In 47 patients with CRC, the primary tumors and the corresponding LMs were investigated. Lymphangiogenesis (LMVD), lymphovascular invasion (LVI), lymphatic vascular endothelial growth factor C expression (VEGF-C) were investigated, Results: A significant correlation was observed between LMVD and LVI in CRCs (p=0.001) as well as in LMs (p=0.0001). LMVD in CRC correlated significantly with that in LMVD-LMs (p=0.026) and LVI in LMs (p=0.036). Survival analysis reveilled a significant difference in disease free and overall survival between patients with and without VEGF-C expression in LMs (p=0.0019 and p=0.0101, respectively)., Conclusion: Our data provide evidence for an important role of lymphangiogenesis in liver metastasis of CRC and provide further support for a possible role of a lymphatico-venous metastatic pathway.