CD34, cytokeratin (CK) 19, cytokeratin (CK) 20, and Ki67 have been demonstrated to be involved in tumor invasion and angiogenesis. The aim of this study was to analyze the clinicopathological significance of CD34, CK19, CK20, and Ki67 expressions in colorectal cancer (CRC) and to evaluate their involvement in the progression of CRC. CD34, CK19, CK20, and Ki67 expressions were assessed in paraffin-embedded specimens collected from 152 cases of CRC and 30 paired normal colorectal tissues by immunohistochemistry. The relationships between CD34, CK19, CK20, and Ki67 expressions and CRC were evaluated. The association of CD34 and Ki67 protein expressions with the clinicopathological characteristics and the prognosis of CRC were subsequently assessed. CD34, CK19, CK20, and Ki67 expressed highly in CRC tissues relative to normal colorectal tissues. Using immunostaining scoring, a significant correlation of CD34 and Ki67 with the UICC staging and histo-differentiation of CRC was found (P 0.05). Meanwhile, no relationship of CD34, CK19, CK20, and Ki67 with the location of CRC was found (P > 0.05). Patients with high expressions of CD34 and Ki67 had the lowest survival (P < 0.05). The results suggest that concurrent expression of CD34 and Ki67 may be an important characteristic of CRC which may help in the prediction of CRC progression.