The adrenal medulla and the sympathoneural extra-adrenal paraganglia comprise the adrenergic sympathoadrenal neuroendocrine system. The two adrenergic components have common characteristics, but also major differences. The common embryologic ancestry from the neural crest, the secretion of catecholamines, and the potential to produce “ectopic” neuropeptide or amine hormones are identical. The presence of the enzyme phenylethanolamine-N-methyltranferase in the adrenal medulla converts norepinephrine to epinephrine, facilitating the biochemical distinction between paraganglioma and adrenal pheochromocytoma. The separate anatomic locations, the genomic difference, the high frequency of multiple paragangliomas, the young age, and the more aggressive tumor biology are the major differences, in comparison with adrenal pheochromocytoma (Table 32.1).