Objective: To comparatively analyze the application value of molecular detection and traditional screening methods in the early diagnosis of colorectal cancer (CRC), clarify the detection efficacy of molecular detection for early CRC and precancerous lesions, and provide evidence-based support for optimizing early diagnosis strategies in clinical practice. Methods: A total of 200 patients with suspected colorectal lesions admitted to our hospital from January 2025 to January 2026 were selected as the study subjects. Using colonoscopy combined with histopathological examination as the diagnostic gold standard, patients were randomly assigned to an observation group (100 cases) and a control group (100 cases) using a random number table method. The observation group underwent fluorescence in situ hybridization (FISH) molecular detection, while the control group received a traditional screening protocol combining serum tumor markers with fecal immunochemical testing (FIT). Diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared between the two groups. The detection rates of CRC at different stages and precancerous adenomas were analyzed, and screening compliance and missed diagnosis rates were recorded for both groups. Results: Based on pathological results, among the 200 patients, 56 were diagnosed with CRC (33 with stage I-II early-stage cancer and 23 with stage III-IV advanced cancer), 20 with high-grade intraepithelial neoplasia, 41 with low-grade adenomas, and 83 with benign lesions or normal findings. The observation group demonstrated significantly higher diagnostic sensitivity, specificity, PPV, and NPV for CRC compared to the control group (all P < 0.05). The detection rates of early-stage CRC and precancerous adenomas were significantly higher in the observation group than in the control group. Both groups showed high detection rates for advanced CRC, with no significant difference between them (P > 0.05). Screening compliance was significantly higher, and the missed diagnosis rate was significantly lower in the observation group than in the control group (both P < 0.05). Conclusion: FISH molecular detection exhibits superior sensitivity and specificity in the early diagnosis of CRC, with distinct advantages in detecting early-stage cancer and precancerous lesions. It also offers better patient compliance and a lower missed diagnosis rate, making it a preferred option for early screening in high-risk populations for CRC. This approach can complement traditional screening methods and facilitate early diagnosis and treatment of CRC.