Background: Colon cancer is the second most common cancer in developed countries. Activated plateletsplay a key role in inflammation and atherothrombosis, with mean platelet volume (MPV) is an early markerof platelet activation. The aim of the study was to clarify the relevance of MPV in patients with colon cancer.Materials and Methods: We measured MPV levels in 128 patients with colon cancer before and after surgery,and 128 controls matched for age, gender, body mass index (BMI) and smoking status. The odds ratios (ORs) and95% confidence intervals (CIs) for colon cancer were calculated using multivariate logistic regression analysesacross MPV quartiles. Results: Patients with colon cancer had higher MPV compared with controls. Surgicaltumor resection resulted in a significant decrease in MPV levels (11.4 fL vs 10.7 fL; p<0.001). A positive correlationbetween MPV and tumor-nodule-metastases (TNM) stage was found. Furthermore, after adjusting for other riskfactors, the ORs (95%CIs) for colon cancer according to MPV quartiles were 1.000, 2.238 (1.014-4.943), 3.410(1.528-7.613), and 5.379 (2.372-12.198), respectively. Conclusions: The findings show that patients with coloncancer have higher MPV levels compared with controls, and these are reduced after surgery. In addition, MPVwas found to be independently associated with the presence of colon cancer. Further studies are warranted toassess the utility of MPV as a novel diagnostic screening tool for colon cancer.