Background: Colorectal cancer is a leading cause of cancer-related mortality worldwide. Early detection is essential for effective treatment. Cancer-testis antigens, such as MAGE-A3, have been identified as potential biomarkers in cancer progression and therapy. This study aimed to evaluate the mRNA expression of MAGE-A3 in blood samples from patients with colorectal cancer (CRC) and non-malignant colorectal diseases (CRD). Methods: A total of 60 patients (30 CRC, 30 CRD) and 30 healthy controls were included. Ages (16-81), whose samples were collected from the Medical City Directory hospitals (GIT and Liver diseases Teaching hospital, Baghdad Teaching Hospital and Oncology Hospital) from 1st of November 2024 to 31 January 2025. and RNA was extracted using TRIzol™ reagent. Quantitative PCR (qPCR) was used to measure MAGE-A3 expression, normalised for the healthy control group. Statistical comparisons were made between CRC and CRD groups. The proportion of patients exhibiting gene expression levels above one is elevated in CRC. Results: sex distribution was not statistically significant (p>0.05), adenocarcinoma was the dominant type of cancer among such cases, a subgroup of patients (86.7%), The grade was moderately differentiated among the majority of patients (83.3%), MAGE-A3 mRNA expression was higher in CRC than CRD (52.6% vs. 47.4%; Likelihood Ratio = 4.317, df = 1, p = 0.038). Conclusion: MAGE-A3 mRNA expression is markedly elevated in CRC and may serve as a potential diagnostic biomarker for distinguishing malignant from benign colorectal conditions.