Adrenal unilateral macronodular hyperplasia is a rare cause of Cushing's syndrome. We discuss the case of two patients who present Cushing syndrome due to unilateral adrenal hyperplasia. They presented the signs of clinical hypercorticism as well as metabolic, cardiovascular and osteoporotic complications. Both patients presented clinical and laboratory signs of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome with elevated urinary free cortisol (UFC) levels, adrenal computed tomography (CT) scan revealed the appearance of unilateral adrenal adenoma and normal contralateral adrenal gland. Adrenalectomy was performed under laparoscopic surgery; the resected mass was pathologically diagnosed as unilateral nodular adrenal hyperplasia. Unilateral adrenal hyperplasia is a very rare etiology of ACTH-independent Cushing syndrome, often mistaken for adenoma on CT and only pathological examination can confirm the diagnosis.