It is still is still a great challenge to find strong and trustworthy colorectal cancer (CRC) prognostic biomarkers that can be linked to the likelihood of the disease's progression and severity. The purpose of this study was to assess the possible link between serum testosterone (TEST) and the development of CRC and its adverse outcomes in both male and female patients. Despite female patients, results revealed that reduced TEST levels (3.5 (2.9-4.1) ng/mL) were significantly (P<0.05) related to CRC cases compared to healthy controls (4.9 (4.4 5.2) ng/mL) and patients with benign polyps (4.1 (3.8-4.9) ng/mL). Serum TEST had a good ability (AUC=0.755) to differentiate CRC cases from all non-cancer individuals. Serum TEST levels (ng/mL) was significantly affected tumor aggressiveness in male patients including late stages (2.9 (2.2 3.2) vs. 4.1 (4.0-5.1); P=0.0001), lymph node invasion (3.0 (2.2-3.9) vs. 4.0 (3.1-4.7); P=0.001), distant metastasis (3.0 (2.2-3.5) vs. 4.0 (3.1-4.9); P=0.0003), high grades (3.0 (2.2 3.8) vs. 4.0 (3.2-5.1); P=0.0001), and large size (3.1 (2.8-4.1) vs. 4.0 (3.2-5.0); P=0.0783). Serum TEST was also significantly correlated with CEA (r =0.288; P=0.048) in CRC male patients. In conclusion, serum TEST hormone elevated levels appears to be protective against CRC development in male patients. Its reduced levels may be a reliable biomarker for monitoring CRC progression and may be helpful in preventing poor disease outcomes.