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Purpose: Both 18F-fluorodeoxyglucose (18F-FDG) uptake and epidermal growth factor receptor (EGFR) status are prognostic variablesof colorectal cancer (CRC). The aim of this study was to investigate a possible association between 18F-FDG uptake on preoperativepositron emission tomography/computed tomography (PET/CT) and EGFR status in primary CRC. Materials and Methods: Records of 132 patients (66 men and 66 women; mean age=67.1±11.1 years) who underwent 18F-FDG PET/CT for CRC staging and subsequent bowel resection were reviewed. In primary lesions, 18F-FDG uptake was semiquantitativelyevaluated in terms of maximum standardized uptake value (SUVmax), and EGFR status was determined by immunohistochemistry. Associations of clinicopathological parameters and EGFR status were analyzed by Pearson’s chi-square test, multiple logistic regression, and receiver operating characteristic curves. Results: Eighty-six patients (65.2%) showed EGFR expression. SUVmax was significantly lower in EGFR-negative tumors than in EGFR-expressing tumors (10.0±4.2 vs. 12.1±2.1; p=0.012). It was the only significant parameter correlated with EGFR expression (odds ratio=2.457; relative risk=2.013; p=0.038). At the SUVmax threshold of 7.5, the sensitivity and specificity for predicting EGFR expression were 84.9% and 40.4%, respectively (area under the curve=0.624; p=0.019). Conclusion: Preoperative 18F-FDG uptake is slightly correlated with EGFR status in primary CRC. Preoperative SUVmax of 18F-FDG may have a limited role in predicting EGFR expression in such tumors because of its poor specificity.