Aim: To assess the diagnostic value of combined detection of tumor markers CA199, CA242, CEA and CA125 in colorectal carcinoma. Methods: Serum levels of CEA, CA199, CA125 and CA242 were determined in 1628 patients with colorectal cancer, 898 patients with colon polyps, and 750 healthy persons. Results: Serum levels of CEA, CA199, CA125 and CA242 were significantly higher in patients with colorectal cancer than in patients with colon polyps and healthy controls. The sensitivity and specificity of combined detection of the four indicators for the diagnosis of colorectal cancer were significantly higher than those of detection of any single indicator. Patients with stage C and D colorectal cancer had significantly higher serum levels of tumor markers than patients with stage A and B disease (P < 0.05). The level of serum tumor markers had no significant association with tumor pathological type (P > 0.05). Conclusion: Combined detection of CEA, CA199, CA125 and CA242 can help improve the accuracy of diagnosis of colorectal cancer. Higher serum levels of CEA, CA199, CA125 and CA242 are associated with more advanced stage of colorectal cancer. © 2013 Baishideng. All rights reserved.