Ganglioneuromas are extremely rare pediatric tumors of neural crest origin that are composed of mature ganglion cells. Pure ganglioneuromas have never been reported in association with multiple endocrine neoplasia type 2 (MEN2) in humans. The MEN2 syndromes are autosomal dominant syndromes caused by gain of function mutations in the RET proto-oncogene. Multiple endocrine neoplasia 2A (MEN2A) is comprised of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia. Multiple endocrine neoplasia 2B (MEN2B) is characterized by MTC, pheochromocytoma, skeletal abnormalities, neural abnormalities of the gastrointestinal tract, and mucosal neuromas. We report two pediatric patients, one with MEN2A and one with MEN2B, who developed isolated adrenal ganglioneuromas without evidence of pheochromocytomas. Interestingly, two mouse models of MEN2B also exhibit adrenal ganglioneuroma formation. We conclude that ganglioneuroma is a rare but not unexpected finding in the MEN 2 syndromes.