Cushing’s syndrome (CS) is a condition of endogenous hypercortisolism caused by different pathological entities that is classified in two variants: (i) ACTH-dependent CS, due to a corticotroph pituitary adenoma or an ectopic tumor; (ii) ACTH-independent CS, due to a primary adrenal process (tumor or hyperplasia). This evidence concerns the gene POMC and Cushing syndrome due to macronodular adrenal hyperplasia.