Background: The maximum standardized uptake value (maxSUV) on F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) scan of mediastinal (N2) lymph nodes may predict pathology in patients with nonsmall-cell lung cancer. However, the maxSUV varies among PET scanners. Thus, we evaluated the ratio of the maxSUV of the lymph node to the primary tumor at different centers to determine whether it was a universal predictor of lymph node malignancy. Methods: This is a retrospective review of a prospective database. Patients with nonsmall-cell lung cancer, a dedicated FDG-PET with the maxSUV of the primary lung tumor and FDG-avid mediastinal (N2) nodes reported (before therapy), and who underwent lymph node removal were eligible. Results: There were 239 patients with 335 FDG-PET-positive N2 nodes at 14 different PET centers. The median ratio of the maxSUV of the lymph node to the maxSUV of the primary tumor of the pathologically proven malignant nodes was 0.58 (range, 0.32 to 1.61). Benign nodes had a median ratio of 0.40 (range, 0.21 to 1.10, p = 0.02). The median value was similar for all centers except one. Receiver operating characteristics analysis determined the optimal value of the ratio that maximized sensitivity to be 0.56 or greater (+LR 6.6, sensitivity 94%, specificity 72%). Conclusions: The ratio of the maxSUV of the mediastinal (N2) lymph node to the maxSUV of the primary tumor in patients with nonsmall-cell lung cancer predicts mediastinal nodal pathology across different PET centers. When the ratio is 0.56 or greater, there is a 94% chance that the node is malignant. The ratio may take into account the different techniques used at different centers. © 2007 The Society of Thoracic Surgeons.