Background: Colorectal cancer is a significant global health concern, ranking as the second most deadly and third most common cancer worldwide. Early detection and removal of precancerous lesions play a crucial role in preventing cancer development and reducing mortality. Since FDG uptake is not specific for malignancy, incidental increased FDG uptake in the gastrointestinal tract may be challenging to interpret and may require further colonoscopic examination. This study aimed to investigate the features associated with malignant and premalignant pathology in patients with incidental colonic FDG uptake and determine the necessity of colonoscopy for each FDG uptake. Methods: Retrospective analysis was performed on data from patients who underwent colonoscopies between January 2016 and December 2021. Patients with FDG uptake in known colorectal malignancy regions were excluded. The study included 56 patients with incidental colonic FDG uptake. PET/CT images were visually and quantitatively analyzed, and the corresponding colonoscopy and histopathological results were recorded. Statistical analyses were conducted to evaluate the relationship between FDG uptake patterns, SUVmax values, and histopathological diagnoses. Colonoscopic findings were categorized as malignancy, polyps, and non-neoplastic lesions. Results: Among the 56 patients with incidental colonic FDG uptake, 36 lesions were identified, and histopathology revealed malignancy in 10 (17.9%) patients and premalignant polyps in the 26 (46.4%) cases. Focal FDG uptake with corresponding wall thickening or soft tissue density on CT was associated with a higher likelihood of premalignant or malignant lesions. The SUVmax values demonstrated a significant difference between negative findings and polyps/malignancies. However, no significant difference was observed between malignant and premalignant lesions. A ROC curve analysis was made and assesed a cut-off value of 11.1 SUVmax (sensitivity: 83.3% and specificity: 90%) to distinguish premalignant or malignant lesions from non-malignant lesions. Conclusion: Incidental colonic FDG uptake with a focal pattern and corresponding CT findings were more likely to indicate premalignant or malignant lesions. SUVmax values were helpful in predicting the presence of pathological findings, but histopathological verification remains necessary for a definitive diagnosis. These findings contribute to our understanding of the clinical implications of incidental colonic FDG uptake and highlight the importance of follow-up colonoscopy for further evaluation.