Cushing syndrome (CS) is a rare disease resulting from glucocorticoid excess. While adrenocorticotropin (ACTH)-dependent Cushing’s disease is more common in adult and adolescent, adrenal tumor is the more typical cause of CS in infants and small children. ACTH-independent adrenocortical hyperplasia causes pediatric CS and can be associated with various diseases and genetic defects. We present an unusual case of 44 month old female with patchy pigmentation in lips and conjunctiva, who was diagnosed as CS. She presented excessive weight gain with growth failure, moon face, hypertension and mood change. Whereas her symptoms and signs of glucocorticoid excess were very prominent and cortisol levels in blood and urine were increased significantly, her computed tomography of adrenal gland showed mild thickening of both adrenal glands. Gross specimens of both adrenal glands after bilateral adrenalectomy were normal size without definitive pigmentation and microscopic exam revealed adrenocortical hyperplasia. After bilateral adrenalectomy, there was no symptom or sign suggesting Nelson syndrome with replacing hydrocortisone and fludrocortisone. Screening for Carney complex, including tumor in heart or thyroid gland and mutation in PRKAR1A gene, was all negative. However during the following-up, multiple osteoblastomas were developed in femur, pelvis and skull base. This case highlights the importance of verifying the etiology of CS and careful following-up and screening for associated diseases.