Early detection is essential to reduce cancer mortality worldwide, including rectal cancer. One factor positively correlated with the incidence of rectal adenocarcinoma is the ABO blood group antigen. However, the use of the ABO antigen as a biomarker in colon cancer screening has not been widely studied. This study aimed to analyze the relationship between the expression of ABO blood group antigens in patients with rectal adenocarcinoma based on the immunohistochemical method. The research was conducted using a cross-sectional study method. The expression of ABO blood group antigens in rectal tissue of the patients with rectal adenocarcinoma was analyzed using the immunohistochemical method (streptavidin-biotin-peroxidase method). Rectal tissue was used as a control without tumor (normal rectal tissue). Statistical data analysis used gamma & Somers correlation and Wilcoxon comparison test. There was a significant difference in the expression of ABO blood group antigens in the rectal tissue between the tumor patient group and the control group (p-value = 0.004). There was no significant correlation between gender, age, stage of adenocarcinoma, histopathological degree of adenocarcinoma, and ABO blood group with the degree of antigen expression of tissue ABO blood group. These results were seen in both the control and tumor group (all p values > 0.05). In conclusion, the expression of the ABO blood group antigen in rectal tissue does not correlate with the tumor stage. However, this antigen can potentially be used as a marker of a malignant process.