The unusual case of a 37 year old woman with Cushing's disease in whom the only feature of hypercortisolism was a clinically asymptomatic osteoporosis is presented. After successful treatment of the disease, serial bone biopsy examinations and bone mineral density measurements (BMD) were performed up to 31 months. 27 months after cessation of hypercortisolism, BMD remained unchanged and histomorphometric examination showed no improvement of the osteopenia in addition to focal osteomalacia. Despite 5 months of calcium and vitamin D therapy, BMD did not improve. This case report emphasizes the importance of routine evaluation of adrenal function in unexplained isolated osteoporosis. Long-term follow-up studies, leaded in a large number of patients are necessary to elucidate the course of osteoporosis in Cushing's syndrome and the usefulness of a specific treatment.