The use of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) in the field of oncology is rapidly evolving; however, (18)F-FDG is not tumor specific. Aside from physiological uptake (18)F-FDG also may accumulate in benign processes. Knowledge of these (18)F-FDG-avid nonmalignant lesions is essential for accurate PET interpretation in oncologic patients to avoid a false-positive interpretation. Through the systematic review of the reports of PET/computed tomography (CT) studies performed in oncologic patients during a 6-month period, we found benign nonphysiological uptake of (18)F-FDG in more than 25% of studies. In half of these, (18)F-FDG uptake was moderate or marked in intensity, similar to that of malignant sites. A total of 73% of benign lesions were inflammatory in nature, with post-traumatic bone and soft-tissue abnormalities (including iatrogenic injury) and benign tumors accounting for the remainder. The differentiation of benign from malignant uptake of (18)F-FDG on PET alone may be particularly challenging as a result of the low anatomical resolution of PET and paucity of anatomical landmarks. Fusion imaging, namely PET/CT, has been shown to improve not only the sensitivity of PET interpretation but also its specificity. Aside from better anatomical localization of lesions on PET/CT, morphological characterization of lesions on CT often may improve the diagnostic accuracy of nonspecific (18)F-FDG uptake. Correlation with CT on fused PET/CT data may obviate the need for further evaluation or biopsy in more than one-third of scintigraphic equivocal lesions. Familiarity with (18)F-FDG-avid nonmalignant lesions also may extend the use of (18)F-FDG-PET imaging beyond the field of oncology. We have tabulated our experience with benign entities associated with increased (18)F-FDG uptake on whole-body PET/CT from 12,000 whole-body (18)F-FDG-PET/CT studies performed during a 4-year period.