Objective To study the expression and significance of the vascular endothelial growth factor (VEGF) and hypoxia induced factor-2 (HIF-2) in benign and malignant adrenal pheochromocytomas.Methods Specimens of 11 normal adrenal glands,24 benign adrenal pheochromocytomas and 11 malignant pheochromocytomas were selected from 1998 to 2008.The expression of VEGF and HIF-2 was detected by immunohistochemistry and in situ hybridization.Results The same results were observed by immunohistochemistry and in situ hybridization.The expressions of VEGF and HIF-2 were negative or doubtful positive in normal adrenal tissues and negative or only weakly positive in benign adrenal pheochromocytomas,with no significant difference between normal adrenal tissue and benign adrenal pheochromocytoma (P＞0.05).The expressions of VEGF and HIF-2 were positive or strong positive in all malignant pheochromocytomas,with significant difference contrast to normal group and benign adrenal pheochromocytomas (P ＜ 0.05).Conclusions mRNA transcription and protein expression of VEGF and HIF-2 are significantly higher in malignant pheochromocytoma tissue than those in benign adrenal pheochromocytoma tissue and normal tissue.The co-detection of VEGF and HIF-2 may be helpful to distinguish benign and malignant pheochromocytomas.