PURPOSE: Despite the similar lymph node metastasis observed in patients with advanced colorectal cancer (CRC), there was a different clinical outcome. The relationships between tumor-related gene expression and prognostic factors such as tumor budding, tumor nodule and extracapsular extension (ECE) of lymph nodes in patients with CRC remain unclear yet. The purpose of this study was to evaluate the relationship between expression of molecular markers such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), matrix metalloproteinases (MMPs) and E-cadherin and the tumor budding, tumor nodule and ECE of lymph nodes in patients with stage III CRC. METHODS: The tissue of 87 patients with stage III CRC were investigated for expressions of molecular markers using immunohistochemical methods. RESULTS: VEGF and MMP-9 expression in tumor tissue were positively associated with the colorectal cancer prognostic factors such as tumor budding, tumor nodule and extracapsular lymph node extension (P<0.05). But, MMP-2, EGF and E-cadherin expression were of no value with regard to them. CONCLUSION: Our results suggest that molecular markers, in particular VEGF and MMP-9, may provide additional prognostic information regarding tumor budding, ECE and tumor nodule.