Objective and aims The primary aim of this study was to evaluate the correlation between incidental focal colorectal foci on fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) with colonoscopic and histopathological results. The secondary aim was to determine to what extent these findings led to a change in patient management. Materials and methods A retrospective study was performed among 5850 patients who had an FDG-PT/CT scan from July 2015 to July 2018. Among these patients, we identified patients with a PET/CT description of incidental colorectal FDG uptake, and a colonoscopy within 90 days from the PET/CT scan. PET/CT findings were compared with colonoscopy-detected lesions and eventually histopathology on a per-lesion analysis and a per-person analysis. Results A total of 145 patients were included in the study. A total of 180 foci of colorectal FDG uptake were detected on FDG-PET/CT. Of these, 86 foci corresponded to advanced colorectal neoplasia (ACRN), positive predictive value (PPV) 47.8%; 95% CI: 40.5–55.1%). On a per-patient analysis 81 patients had a least one ACRN at colonoscopy (PPV 55.9%; 95% CI: 47.6–63.8), this group included 20 patients (13.8%) diagnosed with cancer. There was a small positive correlation between focal FDG-uptake and the finding of ACRN at the same colonic segment at colonoscopy, which was statistically significant, rho = 0.2565, p = .002. The findings changed patient management in 67 (46.2%) cases. Conclusions Incidental focal colorectal FDG uptake on PET/CT is associated with a high risk of ACRN and is affecting subsequent patient management. Further evaluation with colonoscopy is recommended when the patient is considered suitable for further treatment.