We herein report two cases involving a mother and daughter who presented with clinical features of Cushing's syndrome (CS) at 50 and 29 years of age, respectively, and were both found to have adrenocorticotropic hormone-independent adrenal adenoma. Furthermore, a new adenoma was detected in the contralateral adrenal gland in the mother 10 years after surgical treatment, when she presented with subclinical CS. The pathogenesis of this disorder, including the presence of unknown genetic abnormalities causing hereditary CS, is currently poorly understood. In this report, we describe our experience with and consider the pathophysiological implications of two rare and very interesting cases of familial CS.