Colorectal cancer (CRC), the second most fatal cancer and the 3rd most common cancer is expected to cause 0.9 million deaths globally in 2025. Carcinoembryonic antigen (CEA) is currently used in the follow-up of patients with colorectal cancer, and in this study, we are trying to find a better marker than CEA in following up on patients' health and knowing the effectiveness of the treatment used and as a diagnostic marker for colorectal cancer. To determine the significance of Cancer antigen 72-4 (CA72-4) as a prognosis predictor in patients with colorectal cancer, compare its prognostic validity to the CEA biomarker. this case-control study includes (150) participants, 100 patients (59 males and 41 females), and 50 healthy controls (26 males, 24 females). Blood samples were collected from all participants to measure the serum concentrations of CA72-4 and CEA using an enzyme-linked immunosorbent assay (ELISA). Between November 2020 and February 2021 in Baghdad, Iraq, this investigation was conducted at the oncology teaching hospital's gastrointestinal consulting clinic. There was a strong positive relation between CA242 and CEA (R = 0.953, p <0.001) and participants with colorectal cancer had considerably greater levels of CA72-4 than healthy controls (p <0.001). AUC was 0.944, sensitivity was 86%, specificity was 94%, and the cutoff value was 50 U/ml for the CA72-4. while AUC was 0.919, sensitivity was 91%, specificity was 80%, and the cutoff value was 5 ng/ml for the CEA.CA72-4 can serve as a potential prognostic and diagnostic biomarker for colorectal cancer.