The occurrence of a giant myelolipoma of the adrenal gland is reported in a patient with congenital adrenal hyperplasia (21-hydroxylase deficiency). Associated significant findings include a massive proliferation of adrenocortical cells as an integral part of the myelolipoma and a coincidental tumor of the interstitial cells of the testis. The clinical, radiologic, endocrinologic, and pathologic features of this case are correlated with a review of the literature. Three additional myelolipomas are also reported here for the first time. Similar lesions have been induced experimentally in rats and provide further evidence suggesting a hyperplastic rather than a neoplastic nature for this complex lesion, at least in its earlier stages.