Background :Colorectal carcinoma (CRC) is the third most common human cancer. Twist, a basic helix-loop-helix (bHLH) transcription factor, is an epithelial-mesenchymal transition ((EMT) inducer that has been involved in carcinogenesis and chemoresistance. Also, the enhancer of Zeste homolologue2 (EZH2), a member of the polycomb group of genes, had been associated with poor prognosis in several malignancies. Objective :To evaluate the expression of Twist1 and EZH2 in colon carcinoma in Egyptian patients and its relation to clinico-pathological parameters, prognosis, and survival. Methods: Twist1 and EZH2 expressions were evaluated immunohistochemically in 50 cases of colorectal tumors (12 colon adenomas and 38 colon carcinomas) and 20 samples from normal colonic mucosa. Results :The expression of Twist1 and EZH2 was significantly higher in colon adenoma and carcinoma than that in normal colonic mucosa (P< 0.05). Twist1 and EZH2 expressions were associated with decreased tumor differentiation, advanced stage, and lymph node metastasis. Twist1 and EZH2 expressions were significantly related to 3-year disease-free survival (P=0.005 and 0.002 respectively) and 3-year overall survival (P= 0.045 and 0.039, respectively). Conclusions:Twist1 and EZH2 may serve as prognostic predictors for colon carcinoma and may have a potential role as therapeutic targets in patients with colon carcinoma in the future.