Objective: Benign and malignant pulmonary nodules (SPN) are usually differentiated by a 18F-FDG PET standard, i.e., standardized uptake value (SUV) of 2.5.However, there are quite a number of malignant SPNs with poor 18F-FDG uptake will be misdiagnosed by this standard.The aim of this research is to evaluate 18F-FDG PET/CT in diagnosis of SPNs with SUV <2.5.Methods: Fifty-two patients with SUVmean <2.5 SPN (without benign calcification) were researched retrospectively.All patients underwent 18F-FDG PET/CT scan after injection of 18F-FDG 1 hour (early scan) and 2 hours (delay scan).The uptake of 18F-FDG was graded semiquantitatively (SUVmean, SUVmax, △SUVmean, △SUVmax) and visually (absent, faint,moderate, or intense uptake, compared with mediastinum).On the other hand, the density and size of SPN was also analyzed on CT.Final classification of every SPN was based on histopathologic findings or at least 24 months clinical follow-up.Results: There were 39 malignant SPNs (8 bronchioloalveolar carcinomas, 16 adenocarcinomas, 4 partly bronchioloalveolar carcinomas and adenocarcinomas, 1 squamous cell carcinoma,10 with unknown pathology types) and 13 benign ones (2 tuberculomas,3 inflammatory nodules, 1 sclerosing hamangioma,7 with unknown pathology).Although △SUVmax of benign SPNs was significantly lower than that of malignant SPNs, (0.06±0.19 and 0.24±0.36, respectively, p=0.032),other SUVs of benign SPNs had lower tendency compared with those of malignant SPNs, without statistical significances: Early SUVmeans were 1.21±0.65 and 1.30±0.21 in benign SPNs and malignant SPNs, respectively (p>0.05), early SUVmaxs were1.74±1.22 and 1.91±1.03, respectively (p>0.05), delay SUVmeans were 1.45±1.02 and 1.59±0.89, respectively (p>0.05),delay SUVmaxs were 1.97±1.46 and 2.41±1.56, respectively (p>0.05), △SUVmeans were 0.10±0.24 and 0.22±0.36, respectively (p>0.05).Of 9 absent FDG uptake SPNs, there were 5 benign SPNs and 4 malignant SPNs.Of 20 faint FDG uptake SPNs, there were 3 benign SPNs and 17 malignant SPNs.Of 7 moderate FDG uptake SPNs, there were 1 benign SPNs and 6 malignant SPNs.Of 16 intense FDG uptake SPNs, there were 4 benign SPNs and 12 malignant SPNs.No statistical difference between benign and malignant SPNs was found, P>0.05.There were 36 solid SPNs (9 benign and 27malignant), 12 ground-glass opacity SPNs (4 benign and 8 malignant) and 4 partly-solid SPNs (all malignant).There was no statistical difference between benign and malignant SPNs in CT density(P>0.05).The diameter of benign and malignant SPNs were 1.36±0.45cm、 1.42±0.45cm(P>0.05).By Comprehensive analysis of CT characteristics, FDG uptake and △SUVmax of SPNs, the sensitivity, specificity, accuracy, the positive and negative predictive values of 18F-FDG PET/CT in clinically diagnosis of malignant SPNs with SUVmean <2.5 were 94.9%, 46.2%, 82.7%, 84.1% and 75%, respectively.Conclusions : The results demonstrated that there is a higher rates of malignant SPNs in SPNs with SUV <2.5 by FDG PET/CT.Pure depending on the 2.5 standard will lead misdiagnosis in these SPNs group.△SUVmax may be more useful in differential diagnosis of malignant SPNs from the benign ones in SPNs with SUV <2.5.Comprehensive analysis of both FDG PET and CT may improve 18F-FDG PET/CT accuracy in SPNs with SUV <2.5.