Red blood cell distribution width (RDW) indicates the heterogeneity in the size of circulating red blood cells. Increasing studies showed that RDW may be a diagnostic and prognostic marker in various tumors. To investigate the value of RDW as a biomarker in the diagnosis and prognosis of colorectal cancer (CRC), we evaluated 783 newly diagnosed CRC patients, 463 colorectal adenomas (CA) patients, and 331 healthy controls from June 2015 to October 2017 at Fujian Medical University Union Hospital. We found that RDW levels were significantly higher in CRC groups compared with both the CA and healthy control groups (P<0.001). Receiver-operating characteristic (ROC) analysis showed that the area under the ROC curve (AUC) for RDW, CEA, and CA19-9 was 0.643, 0.742, and 0.629 in discriminating CRC patients from healthy controls, respectively. When RDW cut-off value of 13.95 was applied, we distinguished CRC patients from healthy controls with a sensitivity of 41% and a specificity of 94%. Moreover, combined detection of RDW, CEA, and CA19-9 appeared to be a better diagnostic performance with a sensitivity of 56% and a specificity of 99%. However, RDW had little diagnostic value in the differential diagnosis between CRC patients and CA patients. More importantly, RDW levels were significantly associated with TNM stage, pT stage, pM stage, and tumor size among CRC patients. Overall, our study suggested that RDW might be an auxiliary biomarker for diagnosis and prognosis of CRC.