Background: Diagnostic tests that can accurately differentiate between benign and malignant adrenal lesions are lacking. Mass size is currently utilized as an indication for adrenalectomy in patients with adrenal masses. However, the accuracy of this criterion and the ideal size threshold are unclear. The aim of the present study was to determine the frequency of using mass size as the only indication for adrenalectomy and the ideal size threshold for distinguishing malignant primary adrenal tumors from lesions that do not require surgical resection. Patients and Methods: The adrenalectomy database of the University of Wisconsin was retrospectively reviewed. Patients undergoing adrenalectomy for adrenal mass lesions were identified. Student's t-test and Fisher's exact test were used to compare continuous and noncontinuous variables respectively, with P ≤ 0.05 representing significance. Results: Of 198 adrenalectomies performed between 1989 and 2007, 106 met inclusion criteria. There were no differences in age or gender distribution between patients with malignant and benign lesions. After complete clinical, imaging, and biochemical evaluation, mass size was the only indication for 16 adrenalectomies (15.1%). Adrenal mass size in these patients ranged from 3.3 to 14cm (mean 5.9 ± 0.6cm). Only three of these lesions (18.8%) proved malignant. In total, eight malignant tumors were identified in this series (7.5%, size range 4-14cm, mean 8.0 ± 1.3cm). Benign and non-neoplastic lesions accounted for the remaining masses (92.5%, size range 0.7-9.3cm, mean 3.6 ± 0.2cm) and were significantly smaller than malignant lesions (P < 0.001). Conclusion: Adrenal mass size is the only indication for adrenalectomy in a substantial number of patients. A size cut-off of 4cm would have led to resection of all primary malignant adrenal tumors in this series and reduced the number of adrenalectomies for benign disease. © 2009 Elsevier Inc. All rights reserved.