To illustrate the role of radiopharmaceuticals in characterizing non-hypersecreting adrenal masses, 56 patients with non-hypersecreting unilateral adrenal tumors detected on CT and/or MR underwent adrenal scintigraphy. A total of 83 radionuclide studies was acquired; in particular, 24 patients underwent nor-cholesterol scan, 23 patients had metaiodobenzylguanidine (MIBG) imaging, 26 patients had deoxyglucose (FDG) studies and 10 patients underwent somatostatin analogs (SAs) examinations. Histology (n=32) or biopsy (n=24) were obtained; lesions were 19 adenomas, 4 cysts, 1 myelolipoma, 1 neurinoma, 2 ganglioneuromas, 5 benign pheochromocytomas, 4 pseudotumors, 6 carcinomas, 2 sarcomas, 1 fibro-histiocytoma and 11 metastases. For nor-cholesterol, sensitivity, specificity and accuracy for detection of adenoma were 100%, 71% and 92%, respectively; positive predictive value (PPV) was 89%, while negative predictive value (NPV) was 100%. For MIBG, sensitivity, specificity and accuracy for detection of pheochromocytoma were 100%, 94% and 96%, respectively; PPV was 83%, while NPV was 100%. For FDG, sensitivity, specificity and accuracy for detection of malignancies were 100%, 100% and 100%, respectively; PPV and NPV were 100%; furthermore, in 7 patients with malignant adrenal tumors, FDG imaging scan was able to reveal extra-adrenal tumor sites (n=29). For SAs, sensitivity, specificity and accuracy for detection os Sas receptors were 80%, 100% and 90%, respectively; PPV was 100%, while NPV was 83%. In non-hypersecreting adrenal masses, nuclear imaging using specific labeled radiopharmaceuticals such as nor-cholesterol, MIBG, FDG and SAs may provide functional information for tissue characterization. Nor-cholesterol and MIBG scans are able to identify benign tumors such as adenoma and pheochromocytoma respectively, while FDG and SAs imaging allow the recognition of malignant adrenal lesions. Thus, adrenal scintigraphy is recommended for tumor diagnosis in non-hypersecreting adrenal masses and, hence, for appropriate treatment planning of such patients, particularly when CT and/or MR findings are uncertain as well as inconclusive for lesion characterization.