Abstract. The aim of this study was to evaluate the clinical application of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for the detection of malignant lesions. A total of 132 patients with increased levels of blood tumor markers but without a prior history of malignancy were examined. The results of FDG-PET and conventional work-up (CWU) including computed tomography (CT), ultrasonography, radionuclide bone scintigraphy and endoscopy were compared. The final diagnosis was based on pathological evidence, other medical imaging results and a follow-up of at least 6 months. There were 61 patients with malignant lesions and 71 without (benign lesions, n=35; healthy individuals, n=36). The average number of elevated tumor markers and the average increase in these tumor markers were greater in the malignant group than in the non-malignant group. FDG-PET imaging revealed that the maximum standardized uptake value (SUVmax) of the major lesion in patients with malignant (n=61) and benign (n=35) tumors was not significantly related to increased levels of tumor markers (r=0.10, p<0.05). In patients with malignant lesions and an SUVmax ≥3.0, the diagnostic sensitivity, specificity, accuracy, positive predictive value and negative predictive value of FDG-PET were 95.1, 83.1, 88.6, 82.9 and 95.2%, respectively. CWU identified 61 (100%) true-positive patients. No statistically significant differences in sensitivity were observed between the results of FDG-PET and CWU (p>0.05). In 36 healthy subjects without abnormal CWU findings, no abnormal FDG accumulation was revealed by FDG-PET imaging. In conclusion, FDG-PET imaging is a valuable tool for the detection of malignant lesions in patients with increased levels of blood tumor markers but without a history of malignancy. It is therefore reasonable to apply FDG-PET imaging in situations in which the results of CWU are inconclusive, or when patients wish to limit the number of examinations they must undergo.