Malignant mesothelioma usually presents with diffuse involvement of the pleura or peritoneum. Circumscribed or localized malignant mesothelioma has been described in these locations, as well as the viscera, in which case it may cause diagnostic confusion with other, more common entities. Herein, we describe the first well-documented case of primary intrapancreatic malignant mesothelioma in the English literature. The patient was an otherwise healthy 39-year-old woman who presented with a symptomatic mass in the head of the pancreas that was completely resected via pancreaticoduodenectomy. The tumor was composed of cysts, papillae, and tubules lined by cells with abundant eosinophilic cytoplasm and immunohistochemically expressed CA-125, calretinin, and D2-40. Follow-up revealed no evidence of residual or recurrent disease 32 months after surgery. This report also describes the clinical and pathologic characteristics of an intrapancreatic mesothelioma and provides a review of the literature regarding entities that may be considered in the differential diagnosis of this tumor.