Lung cancer staging using the International System for Staging Lung Cancer describes the extent of NSCLC in terms of the size, location, and extent of the primary tumor (T descriptor), the presence and location of lymph node involvement (N descriptor), and the presence or absence of distant metastatic disease (M descriptor). Radiologic evaluation and interpretation are important components of the clinical staging evaluation and can greatly influence whether the patient is treated with surgical resection, radiation therapy, chemotherapy, or a combination of these modalities. Common imaging modalities for staging lung cancer are chest radiographs, CT, MRI, PET and fused PET/CT. The most common radiologic examination in the lung cancer patient is chest CT because of its ability to provide anatomical information regarding the primary tumor as well as evaluate the extent of mediastinal and extrathoracic disease. In addition, whole body positron-emission tomography (PET) using 18-fluorodeoxyglucose (FDG), especially fused PET/CT has become an important correlative imaging study for staging lung cancer. The application of PET/CT and its interpretation in the clinical staging of mediastinal lymph nodes is the focus of this discussion. CT is useful for anatomic identification of mediastinal lymph nodes, but is limited in evaluating metastatic involvement of the lymph nodes. Meta-analyses review of staging NSCLC with CT indicates the limitations of CT for staging the mediastinum. In one review by Dales et al of 42 studies, there was a combined sensitivity of 83%, a specificity of 82%, and an accuracy of 80%. Dwamena et al reviewed 29 studies and reported a combined sensitivity of 60%, specificity of 77%, and accuracy of 75%. This limitation is primarily because CT only shows the size, shape and location of mediastinal lymph nodes, not the biologic activity. PET imaging with FDG, which demonstrates metabolic activity, has been shown to be more accurate (reported accuracy, 81% - 96%) than CT and MRI in the detection of nodal disease. PET is also useful in differentiating hyperplastic nodes from metastatic nodes and for detecting metastasis within normal size nodes. In the meta-analysis of nodal staging by Dwamena, the sensitivity of PET was 79% and specificity was 91% compared to 60% and 77% for CT (41). Fused PET/CT imaging provides registration of FDG metabolic activity with anatomic detail of CT and has been reported to be more accurate than PET or CT alone in staging patients with NSCLC. Antoch et al reported that the accuracy for detecting metastatic mediastinal lymph nodes was 63% for CT alone, 89% for PET alone, and 93% for PET/CT, while the sensitivity and specificity was 89% and 94% for PET/CT, 89% and 89% PET, and 70% and 59% for CT. The improvement in mediastinal staging with PET/CT continues to be supported in the literature; a recent report by Kim et al in Cancer, 2007, indicates PET/CT mediastinal nodal; staging in 674 patients to have a sensitivity of 61%, specificity of 96% and accuracy of 86%. Assessment of mediastinal adenopathy for radiation oncologist is also important because involved nodes are included in their treatment plan. CT done for radiotherapy treatment planning is usually done without contrast, and many of these patients will not undergo mediastinoscopy; fused imaging for metabolic tumor localization and an experienced radiologist interpretation of metastatic nodal disease are important. PET/CT is reported to alter the radiation therapy treatment plan in more than 50% of patients with NSCLC when compared to CT alone. Fused imaging can also be used to differentiate suspected metastatic disease from benign lesions and to help differentiate recurrent tumor from radiation changes.