Purpose: To critically analyze the role, accuracy and safety of percutaneous adrenal biopsy for indeterminate adrenal lesions. Materials and Methods: Adrenal biopsies were performed in 15 among 214 patients (7%) diagnosed with adrenal masses being indeterminate on preoperative imaging. Definitive histopathology was obtained in all and overall sensitivity and negative predictive value were calculated. Safety of the procedure was reported. Results: The study included 8 male and 7 female patients with a mean age of 33.3 ± 20.3 years (range 7–65). Biopsy was carried out under computed tomography and ultrasound guidance in 12 and 3 patients, respectively. There were 2 nonrepresentative biopsies that were proved to be adrenocortical carcinoma and myelolipoma after adrenalectomy. Results of biopsy in the remaining 13 patients provided accurate diagnosis as proved by definitive histopathology in all but 2 in whom the final diagnosis was established as adrenocortical carcinoma while biopsy was paraganglioma in one and cortical adenoma in the other. Overall sensitivity and negative predictive value of adrenal biopsy was 73.3 and 60%, respectively. Apart from two mild hypertensive episodes following silent pheochromocytoma biopsy, no complications were reported. Conclusions: Percutaneous biopsy is a safe procedure for the diagnosis of pathologic conditions of the adrenal gland with a reasonable diagnostic aid.