OBJECTIVE To discuss the etiology, diagnostic criteria and treatment of Nelson's syndrome. METHODS Twenty-three patients with Nelson's syndrome who were treated in our department over the last 19 years were analyzed retrospectively. Removal of adenoma by the transsphenoidal approach was done in 21 patients and by transfrontal craniotomy in 2. The follow-up period ranged from six months to nine years. RESULTS The incidence of Nelson's syndrome was 7.7% in a series of 300 patients with Cushing's disease treated by microsurgery in the same period. Hyperpigmentation was relieved and adrenocorticotropic hormone (ACTH) levels decreased in all patients after tumor excision. Eight patients with visual disturbance improved after surgery. The curative and remission rates were 56.5% and 26.1%, respectively. CONCLUSIONS Transsphenoidal microsurgical removal of pituitary ACTH adenoma is the first choice in the prevention and treatment of Nelson's syndrome. Regular follow-up examinations should be performed over a long time.