Adrenocortical carcinoma is a rare tumor associated with a commonly poor prognosis. However, data on the natural history and response to therapy of patients with this malignancy have often been conflicting. Our objective of this retrospective study was to evaluate the clinical course and survival of patients with adrenocortical carcinoma and to identify relevant prognostic factors. Between 1966 and 1996, 31 patients with histologically documented adrenocortical carcinoma were observed at the Lahey Clinic Medical Center. Patient information was obtained from chart review. At the time of diagnosis, 48 per cent of patients had endocrine symptoms with compatible hormonal studies, 19 per cent had involvement of the inferior vena cava by tumor thrombus, and 32 per cent had metastatic disease. The median survival time was 17 months (range, 1-205 months) for the entire group, and the 5-year survival rate was 26 per cent. Age <54 years, absence of metastatic disease at the time of diagnosis, and completeness of surgical resection were associated with better prognosis. Evaluation of survival with the Cox proportional hazards model suggested that age <54 years, absence of metastatic disease, and nonfunctioning tumor status were independently associated with improved survival. The prognosis of patients with adrenocortical carcinoma is poor but appears more favorable in patients <54 years, with localized disease, or nonfunctioning tumor status. Complete tumor resection may be associated with improved survival.