This study was designed to evaluate the sensitivity, specificity, and predictive accuracy of PET-FDG imaging in detecting metastatic disease involvement of adrenal glands in patients with lung cancer. We wanted to compare efficacy of positron emission tomography (PET)-fluorodeoxyglucose (FDG) imaging to computed tomography (CT) scanning in differentiating benign from malignant involvement of adrenal glands in patients with lung cancer. Thirty patients with biopsy-proven lung cancer and abnormal findings on PET and/or CT scanning were studied for presence of adrenal abnormality suggestive of metastatic disease involvement (n = 26) or benign adrenal enlargement (n = 4). The results of PET and CT scanning were compared to histological findings and/or clinical follow-up for at least 1 year for presence or absence of adrenal metastases. PET-FDG imaging correctly detected the presence of metastatic involvement in 17 of 18 patients and excluded metastatic involvement in 11 of 12 patients for sensitivity, specificity, and accuracy of 94.4%, 91.6%, and 93.3%, respectively. CT scanning showed enlarged adrenals without metastases in 8 of 30 patients and normal-sized adrenals in the presence of metastases in 5 of 30 patients. There was a false-positive PET finding in 1 patient and a false-negative PET finding in another patient. PET-FDG imaging is a highly sensitive, specific, and accurate test to differentiate benign from malignant involvement of adrenal glands in patients with lung cancer and often ambiguous findings on CT scanning.