As observed by other authors, normal adrenal medullary tissue frequently gives an apparently positive meta-iodobenzylguanidine (MIBG) scan in cases studied using 123I-MIBG and less frequently 131I-MIBG. The aim of this study was to assess the usefulness of a scoring system, based on different uptakes of the radiopharmaceutical, to improve the accuracy of 123I-MIBG scintigraphy in patients with either adrenal or extra-adrenal pheochromocytomas. Charts from 67 consecutive patients (29 males and 38 females, median age 48 years, range 14-80 years) with suspected pheochromocytoma (either sporadic or familial: multiple endocrine neoplasia (MEN) 2a, MEN2b, Von Hippel-Lindau, neurofibromatosis type 1) who underwent 123I-MIBG scintigraphy (scans acquired 4-24 h after injection) from 1991 to 2004, were independently reviewed by two experienced nuclear medicine physicians using liver uptake as a reference (scores: 1, uptake absent or less than the liver; 2, equal to the liver; 3, moderately more intense than the liver; 4, markedly more intense than the liver). Interfering medications were discontinued for the appropriate time before MIBG injection. Histological data were obtained for all patients who underwent adrenalectomy. Scintigraphies were classified as positive using the following criteria: extra-adrenal focal uptake, adrenal enlargement together with non-homogeneous uptake and adrenal uptake more intense than the liver (score 3-4). After surgical resection, as confirmed by histological findings and long-term follow-up (range 1-14 years, average 9.25 years), 43 patients were considered true positives using the proposed scoring system, 20 were true negatives, four were false negatives and none was false positive. In conclusion, the proposed scoring system demonstrated high specificity (100%), sensitivity (91.5%) and accuracy (94%) in the management of pheochromocytoma. Positive predictive value and negative predictive value were 100% and 83.3% respectively. Normal adrenal tissue uptake was correctly discriminated from pheochromocytomas in 18 out of 20 patients, with adrenal uptake equal to the liver (grade 2), using the proposed cut-off level.