Background:-Colorectal carcinoma (CRC) is a major cause of morbidity and mortality worldwide. Both calcium-binding protein, S100A4, and the cell adhesion molecule, CD24, have been implicated to play an important role in carcinogenesis and tumor progression in various human malignancies. Aim:-To evaluate the expressionof S100A4 and CD24 in colorectal tumors and their role in development and progression of CRC and correlate their expression with the clinicopathological features. Methods:-S100A4 and CD24 expression was analyzed by immunohistochemistry in paraffin-embedded specimens of colorectal adenomas (n=18) and CRC (n=40). Results:-S100A4 and CD24 expression was detected in 28/40 (70%) and 24/40 (60%) of CRC respectively.The positive expression rates of S100A4 and CD24 were significantly higher in CRC than adenomas (P<0.05). S100A4 was significantly expressed in tumors with high histological grades (P= 0.03).A statistically significant relationship was found between S100A4 and CD24 expression and advanced tumor stage (P= 0.009 and =0.03), lymph node metastasis (P=0.04 and =0.0001) and lymph-vascular space invasion (LVSI) (P=0.02 and =0.008) respectively, but not with the age, gender and tumor size (P>0.05). Conclusion:-S100A4 and CD24 up-regulation may be associated with the development and progression of CRC. Combined detection of S100A4 and CD24 may serve as an indicator of the aggressive behavior and poor prognosis of CRC.