Physicians often are faced with determining benignity or malignancy in solitary pulmonary nodules in order to refer patients appropriately for curative resection of early-stage malignant nodules and to avoid the morbidity and mortality of a surgical procedure for benign nodules. Nodules are easily deemed benign when they are unchanged on chest radiographs over 2 years or have symmetrical patterns of calcification or central fat on chest CT. Similarly, growing, spiculated lesions in older patients with an extensive smoking history or other risk factors for cancer are easily recognized as likely to be malignant. However, solitary pulmonary nodules classified as indeterminate after consideration of radiologic characteristics and patient risk factors have traditionally posed a diagnostic dilemma. The use of newer imaging modalities, including contrast -enhanced chest CT, fluorodeoxyglucose PET, and technetium Tc 99m SPECT, can help distinguish benign nodules from those that are malignant.