Disclosed herein are methods of diagnosing and treating a malignant adrenocortical tumor, including adrenocortical carcinoma. In some examples, methods of diagnosing a malignant adrenocortical tumor include detecting expression of at least one microRNA (miR) gene product, such as miR-100, miR-125b, miR-195, miR-483-3p, miR-483-5p and IGF2 mRNA in a sample obtained from the subject with an adrenocortical tumor and comparing expression of at least one of these miR gene products and IGF2 mRNA in the sample obtained from the subject to a control. Altered expression of at least one of the miR gene products and IGF2 mRNA, such as a decrease in miR-100, miR-125b or miR-195 or an increase in miR-483-3p, miR-483-5p, and an increase in IGF2 mRNA, in the sample obtained from the subject compared to the control indicates a malignant adrenocortical tumor.
