Background: The diagnosis and treatment of pheochromocytoma pose a challenge to physicians. Several trends in the presentation, diagnosis, and surgical treatment of pheochromocytoma have emerged in the last 10 years. The diagnostic accuracy and consequences of misdiagnosis of pheochromocytoma are not well known. We aimed to systemically study the diagnostic accuracy and treatment outcomes of pheochromocytoma and to reveal the causes and consequences of misdiagnosis (including both overdiagnosis and underdiagnosis). Methods: We reviewed the electronic and paper charts of 49 patients who underwent adrenalectomy or adrenal biopsy with either preoperative or pathologic diagnosis of pheochromocytoma in a large academic hospital from 1997 to 2007. Three groups of patients (overdiagnosed, correctly diagnosed, and underdiagnosed) were compared on clinical courses, biochemical tests, imaging studies, and surgical outcomes. Results: Pheochromocytoma was overdiagnosed in 9 patients, correctly diagnosed in 30 patients, and underdiagnosed in 10 patients. The overdiagnosis rate was 23% (9/39), and the underdiagnosis rate was 25% (10/40). The 3 distinct groups of patients exhibited significant differences in clinical presentation, biochemical tests, and imaging characteristics. The most common causes of overdiagnosis were misinterpretation of borderline biochemical test results and overzealous imaging. Overdiagnosis subjected patients to unnecessary adrenalectomy and its complications. The most common cause of underdiagnosis was failure to consider and test for pheochromocytoma. Underdiagnosis resulted in dangerous adrenal biopsy or adrenalectomy with hypertensive crisis and nearly doubled the length of stay in hospital. Surgical resection of correctly diagnosed pheochromocytoma was largely effective and safe, but intraoperative and postoperative complications occurred in some patients. Conclusion: We conclude that misdiagnosis of pheochromocytoma is not uncommon and causes serious adverse effects. Correct interpretation of biochemical tests and imaging is crucial to a correct diagnosis, and pheochromocytoma should always be included in the differential diagnosis of any adrenal mass. Our data suggest that physician education is needed to improve the diagnosis and treatment of pheochromocytoma. © 2009 Elsevier Inc. All rights reserved.