Angiogenesis plays an important role in the progression of colorectal cancer (CRC). Studies have indicated vascular endothelial growth factor (VEGF) is the predominant angiogenic factor. Cyclin D1 (CCND1) induces production of VEGF and is required for migration of blood vessels. Our aim was to determine the roles of CCND1 and VEGF overexpression in CRC patients. We analyzed clinicopathological features, VEGF and CCND1 expressions by immunohistochemical (IHC) staining in 100 stage I-III CRC patients (44 were postoperative relapsed; 56 were postoperative non-relapsed) to determine the correlation between clinicopathologic features and co-existence of CCND1 and VEGF. Furthermore, the clinical outcomes of co-existence of CCND1 and VEGF were investigated. Multivariate analysis showed vascular invasion (P = 0.019), VEGF overexpression (P = 0.033), and high postoperative serum carcinoembryonic antigen (CEA) levels (P = 0.022) were independent predictors of postoperative relapse. Co-existence of CCND1 and VEGF overexpression had significantly poorer disease-free survival rates (P = 0.004) and overall survival rates (P = 0.001) than other phenotypes. Co-existence of CCND1 and VEGF overexpression would potentially assist in TNM staging systems to predict the prognosis of these patients who would benefit from intensive follow-up and therapeutic programs.