Colorectal cancer (CRC) represents the second most common cause of cancer mortality in the western world. The tumors frequently show metastatic spread which affects different organs such as lymph nodes, liver and lungs. Although the pattern of spread may vary, the initial step usually involves dissemination to regional lymph nodes. At present it is clear that neovessel formation, including lymphangiogenesis, represents key events in tumor progression. However, to what extent lymphangiogenesis contributes in the progression of CRC is unclear. This work focuses on recent progress within the field of tumor lymphangiogenesis with special reference to CRC, and on novel therapeutic strategies for anti-lymphangiogenic therapies. Inhibition of metastatic spread may be achieved by restriction of lymphatic vessel growth by using targeted therapeutic strategies towards molecules involved in lymphangiogenic signalling. Such adjuvant therapeutic approaches in addition to existing therapeutic strategies may represent a favourable treatment for CRCs with higher than average risk of disease recurrence and progression. © 2007 Wiley-Liss, Inc.