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Summary: Background: Colorectal cancer is the second commonest cause of cancer mortality. Some countries are implementing colorectal cancer screening to detect lesions at an early stage using non‐invasive tools like the faecal immunochemical test. Despite affordability, this test shows a low sensitivity for precancerous lesions and a low positive predictive value for colorectal cancer, resulting in a high false‐positive rate. Aim: To develop a new, non‐invasive colorectal cancer screening tool based on bacterial faecal biomarkers, which in combination with the faecal immunochemical test, could allow a reduction in the false‐positive rate. This tool is called risk assessment of intestinal disease for colorectal cancer (RAID‐CRC). Methods: We performed both the faecal immunochemical test and the bacterial markers analysis (RAID‐CRC test) in stool samples from individuals with normal colonoscopy (167), non‐advanced adenomas (88), advanced adenomas (30) and colorectal cancer (48). All the participants showed colorectal cancer‐associated symptoms. Results: Performance of the faecal immunochemical test for advanced neoplasia (ie advanced adenoma and colorectal cancer) was determined by using the cut‐off value established in Catalonia (20 µg haemoglobin/g of faeces) for a population‐based screening approach. Sensitivity and specificity values of 83% and 80%, respectively, and positive and negative predictive values of 56% and 94%, respectively, were obtained. When both the immunological and the biological analysis were combined, the corresponding values were 80% and 90% for sensitivity and specificity, respectively, and 70% and 94% for positive and negative predictive values, respectively, resulting in a 50% reduction of the false‐positive rate. Conclusions: RAID‐CRC test allows a substantial reduction in the faecal immunochemical test false‐positive results (50%) in a symptomatic population. Further validation is indicated in a colorectal cancer‐screening scenario. [ABSTRACT FROM AUTHOR]