Early detection of colorectal cancer (CRC) significantly improves overall prognosis and increases 5-year survival rates up to 90%. Current non-invasive screening methods for CRC, such as the Faecal Immunohistochemical Test (FIT), have some drawbacks, namely, low sensitivity and a high false-positive rate. The Sialyl-Tn (STn) antigen, frequently expressed in pre-malignant lesions and adenocarcinomas, has been shown to be detected by the novel monoclonal antibody L2A5. In this study, we explored the potential of L2A5 as a non-invasive CRC screening method in an attempt to overcome current limitations. The subjects were categorised into four groups based on colonoscopy findings: no lesion (NL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and colorectal cancer (CRC). Slot blot analysis using the L2A5 antibody was performed on stool samples from 95 colonoscopy patients. Our findings showed a differential STn expression between the different clinical groups, evidencing excellent discrimination between NL and CRC (AUC, 0.8252; 95% CI: 0.6983–0.9521; sensitivity, 70%). Moreover, moderate discrimination between the NL+LGD and HGD+CRC groups was discerned (AUC, 0.7766; 95% CI: 0.6792–0.8740; sensitivity, 58%). These findings support the application of L2A5 as a tool for detecting STn, allowing for the identification of advanced lesions in non-invasive CRC screening.