BACGROUND: Cancer colon is one of most common cancers worldwide. Colonoscopy; an invasive and costly investigation method is the most reliable tool for diagnosis. Early diagnosis of cancer colon gives a high chance of cure. Fecal M2-PK; a tumor biomarker is a new approach for cancer colon screening. AIM: This study aimed to evaluate fecal M2-PK as a biomarker for cancer colon screening. METHODS: This comparative cross-sectional study included 3 groups. 30 healthy individuals (Group Ι), 50 diagnosed cancer colon patients (Group П) and 20 cancer colon patients who were the only operable patient from Group П (Group ш). For all groups, History and physical examination was done. Fecal M2-PK concentrations were detected by ELISA. RESULTS: The study revealed that there was a significant difference between cancer colon patients and healthy individuals (control) regarding age (p=0.046*), BMI (p=0.004*), history of smoking (p=0.025*), history of low fiber and high protein diet (p=0.001*), and levels of M2-PK (p=0.001*). There was a significant difference in the mean value of M2PK levels in regard to sex (p=0.043*) and site of cancer colon (p=0.002*) only. Cancer colon can be detected with fecal M2-PK with remarkable sensitivity &specificity (98% and 93% respectively). The overall accuracy of M2PK in detecting cancer colon was 96.6%. Conclusion: Fecal M2-PK is considered as a good screening biomarker for cancer colon