Bilateral hilar 18 F-FDG-avid foci are often noted on PET studies of patients without lung cancer. This finding may lead to diagnostic uncertainty about the presence of metastatic disease. Our objective was to evaluate features of these foci associated with benign or malignant etiology. Methods: We performed a retrospective study of patients with cancer with bilateral hilar foci on 1 or 2 sequential 18 F-FDG PET studies between 2002 and 2006. Patients with lung cancer, sarcoidosis, or anthracosis/ silicosis were excluded. Variables evaluated were maximum standard uptake values (SUV max), purity (absence of 18 F-FDGavid foci in nonhilar mediastinal nodes), symmetry (difference between left and right side SUV max), the primary tumor, node size determined by CT, and, in those who participated in 2 studies, stability of uptake over time. The gold standard was histologic diagnosis or long-term clinical follow-up (range, 19-41 mo; mean, 25 mo). Results: Fifty-one patients with the finding of bilateral hilar 18 F-FDG-avid foci underwent a staging-only PET study; 52 scans from an additional set of patients demonstrated this abnormality on at least 1 of 2 sequential studies, the first of which was performed for staging. On univariate analysis, variables associated with malignancy were SUV max (6.6 6 4.1 vs. 3.5 6 1.0 for benign, P , 0.001; t test); impurity (P , 0.001; x 2 test), with 79% of impure scans versus 18% of pure scans being malignant; node size determined by CT (P 5 0.027); and change in uptake between scans 1 and 2 (change in SUV 5 2.7 6 2.1 vs. 0.73 6 1.1 for benign, P , 0.01; t test). Variables associated with benign etiology were: symmetry (difference between left and right sides 5 0.57 6 0.54 for benign vs. 1.8 6 1.7 for malignant, P , 0.01), purity, and colorectal primary (75% of colorectal were benign vs. 34% of breast, 49% of lymphoma, and 37% of other, P 5 0.030; x 2 test). After multivariate analysis, SUV max and purity were found to be independent predictors, with the odds of malignancy increasing by 1.54 (95% confidence interval, 1.16-2.05) for each unit increase in SUV and decreasing by 0.08 (95% confidence interval, 0.03-0.22) if pure. Conclusion: In patients with nonlung cancer, in particular colorectal, foci of symmetric and mild uptake limited to the hilar regions that are stable on 2 sequential PET studies despite intervening anticancer therapy are likely related to a benign etiology.