Little is known about the pathophysiology of sporadic adrenocortical tumors. Benign and malignant adrenocortical tumors are often difficult to distinguish by conventional histology. We tested 38 adrenocortical tumors (23 benign and 15 malignant) for loss of heterozygosity (LOH) at 17pl3 and abnormalities in the 11p15 region (uniparental disomy, UPD, and overexpression of the IGF II gene). We showed that 17p13 LOH, 11p15 UPD and overexpression of the IGF II gene are frequent in adrenocortical tumors, occurring in 40% of them. These genetic changes are associated with the malignant phenotype and thus could be used for diagnostic evaluation of adrenocortical tumors.