Background/Objectives: Gut microbiota interacts with nutrients, which may be relevant to assigning a microbial signature to colorectal cancer (CRC). We aim to evaluate the potential of gut microbiota combined with dietary habits in the early detection of pathological findings related to CRC in the course of a screening program. Methodology: The colonoscopy performed on 152 subjects positive for fecal occult blood test showed that 6 subjects had adenocarcinoma, 123 had polyps, and 23 subjects had no pathological findings. Gut microbiota was analyzed by 16S metagenomic. Caret package was used to build the classification models in R. Results: Random forest (RF) classifier models were used to test the potential of gut microbiota alone or combined with dietary habits as a biomarker to discern between individuals with CRC-related lesions (polyps or adenocarcinoma) versus individuals without pathological findings. RF classifier models yielded an area under the curve of 0.790 using gut microbiota data, 0.710 using dietary habits data, and 0.804 in the combined model including gut microbiota and dietary habits data. The abundance of Suterella, Oscillospirales, Proteobacteria, and Burkholderiales was highly discriminant between groups, together with the consumption of fruit and vegetables and the consumption of carbonated and/or sweetened beverages. Conclusions: Our results suggest that the interaction between gut microbiota and dietary habits is relevant when a microbial signature is used as a marker in CRC. Moreover, gut microbiota signature and information about the dietary habits of the individuals seem to be important for improving screening programs for the early detection of CRC.