Unlike common malignant tumors, malignant pheochromocytomas cannot be definitely diagnosed using histological features. This unique nature of pheochromocytomas provides a valuable model that may promote the investigation of the mechanism of other common malignant tumors where similar frameworks are not available. Studies on malignant pheochromocytomas should benefit not only the individuals with pheochromocytomas but those with other tumors. A review on the development of differentiating diagnosis between malignant and benign pheochromocytomas in imaging studies, biological fluid examinations, pathological examinations, molecular markers and genome studies, was updated in the hopes of guiding the next studies of pheochromcytomas.