INTRODUCTION: Acinar cell carcinoma (ACC) is a rare, malignant neoplasm with a generally poor prognosis. We report our institutional series of 14 patients with ACC to determine current guidelines for their evaluation and treatment. MATERIALS AND METHODS: The Johns Hopkins pathology prospective database was reviewed from 1988 to 2006 to identify patients with pancreatic neoplasms possessing features of acinar cell differentiation. Retrospective review and follow-up was performed for each patient. RESULTS: Fourteen patients with ACC were identified with a median age of 57 years. All patients presented with abdominal pain or discomfort with none showing evidence of lipase hypersecretion syndrome. Each patient underwent surgical resection, including nine pancreaticoduodenectomies and five distal pancreatectomies. Median tumor size was 3.9 cm with 12 patients found to have stage IIB disease or worse. Four patients underwent neoadjuvant chemoradiation. Eight of the fourteen patients developed recurrent disease. Overall median survival and disease-free survival were 33 and 25 months, respectively, as compared to a median survival of 18 months for pancreatic adenocarcinoma. CONCLUSION: Acinar cell carcinomas are rare, aggressive neoplasms that are difficult to diagnose and treat. Operative resection represents the best first-line treatment. These lesions have a better prognosis than the more common pancreatic adenocarcinomas.