PURPOSE: Although stromal-cell-derived factor (SDF)-1alpha is suggested to be involved in tumorigenicity and tumor angiogenesis, the clinicopathological significance of its expression in colorectal cancers is not fully understood. We examined SDF-1alpha expression in colorectal cancers and investigated its relationship to clinicopathological features such as tumor staging, lymph-node metastasis, vascular invasion (VI), lymphatic invasion (LI) and neural invasion (NI). METHODS: Specimens of 83 primary colorectal cancers were examined immunohistochemically, and the relationships between clinicopathological features and SDF-1alpha expression were analyzed. To compare the expressions between the normal colon tissue and colorectal cancer tissues, we performed Western blot analyses. RESULTS: According to the Western blot analyses, SDF-1alpha was more highly expressed in colorectal carcinoma tissues than in normal colonic mucosa (20/21). According to the immunohistochemical stain, SDF-1alpha was associated with nodal status, distant metastasis, tumor staging, VI and LI. SDF-1alpha expression had a significant prognostic value for overall survival. Kaplan-Meier plots of survival in patients with high SDF-1alpha showed that high SDF-1alpha expression was associated with a shorter overall survival. However, no association was found between SDF-1alpha expression and other pathologic or clinical variables, including age, gender, degree of differentiation, and presence of perineural invasion. CONCLUSION: The expression of SDF-1alpha might be associated with tumor progression in colorectal cancer. Inhibition of SDF-1alpha could be a therapeutic option in colorectal cancer patients.