Background: Adrenal tumors affect 3–10% of world population. AQP2 is water channel protein that is widely distributed among mammalian tissues and plays a major role in water homeostasis. However, little is known about the expression and significance of AQP2 in human adrenal tumors. Aim: To evaluate the diagnostic significance of expression of AQP2 in primary adrenal gland tumors,and correlate the results with different clinico-pathological variables. Material and Methods: This is a retrospective, selected, controlled study carried on 44 adrenal gland lesions included (14) adrenocortical adenoma, (10) adrenocortical carcinom and (20) pheochromocytoma. Clinicopathological characteristics of examined cases were correlated with the IHC expression of Aquaporin2 RESULTS: Aquaporin2 IHC expression was more frequent in pheochromocytoma (100%) than in ACA (35.7%) and ACC (40%), (p =>0.001). Among pheochromocytoma , 15% the cases show focal expression(+1), 40% of cases show intermediate expression(+2) and 45% of cses show diffuse expression (+3). Sensitivity and specificity of AQP2 in diagnosis of pheochromocytoma were 100% and 87.5% respectively. CONCLUSION: The results suggested that AQP2 is a diagnostic marker of pheochromocytoma and can differentiate it from adrenocortical adenoma and adrenocortical carcinoma but cannot differentiate between both adrenocortical adenoma and adrenocortical carcinoma.