OBJECTIVE To evaluate long-term morphological, functional, and clinical outcome in adrenal incidentalomas. METHODS A total of 118 patients (77 F and 47 M; age 62.3+/-1.0 years) with adrenal incidentalomas were evaluated at baseline and followed-up for median 3 years (range 1-10 years) by clinical, biochemical, hormonal, and morphological evaluation. Among them, six patients with diagnosis of subclinical Cushing's syndrome (SCS) underwent surgery. RESULTS At entry, 86% (n=102) of tumors were nonfunctioning (NF) and 14% (n=16) showed SCS. Comparing NF with SCS patients, a significantly higher percentage of dyslipidemia was found in the group of SCS patients (50 vs 23%, P=0.033). During follow-up, adrenal function remained normal in all NF patients, none of them developed subclinical or overt endocrine disease. The cumulative risk of mass enlargement was globally low (25%), but progressive up to 8 years. SCS was confirmed in all patients, and none of them shifted to overt Cushing's syndrome. The cumulative risk of developing metabolic-cardiovascular abnormalities was globally low (22%), but progressive up to 8 years and new diseases were recorded in the group of NF patients only (three patients with dyslipidemia, four with impaired fasting glucose/impaired glucose tolerance, and three with diabetes mellitus). SCS patients who underwent surgery did not show any significant clinical improvement. CONCLUSIONS The risk of mass enlargement, hormonal, and metabolic impairment over time is globally low. Conservative management seems to be appropriate, but further prospective studies are needed to establish the long-term outcome of such patients, especially for metabolic status, cardiovascular risk profile and their relationship with endocrine function.