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Molecular analyses of neoplasms of the pancreas, coupled with careful histopathologic examination has helped refine the classification of pancreatic neoplasia. A number of molecularly and histologically distinct subtypes of pancreatic neoplasms have been identified and, importantly, many of these subtypes have important clinical implications. For example, most of the solid-pseudopapillary neoplasms harbor mutations in the β-catenin gene (CTNNB1), and, as a result, most solid-pseudopapillary neoplasms have an abnormal nuclear pattern of labeling with antibodies to the β-catenin protein. Clinically, patients with a solid-pseudopapillary neoplasm have a much better prognosis than do patients with ductal adenocarcinoma of the pancreas. Therefore, the immunolabeling of a pancreatic biopsy for the β-catenin protein can help identify patients with low-risk neoplasms. It is clear that the time is now ripe for a new modern classification of neoplasms of the pancreas; a classification that does not abandon gross and microscopic pathology, but which instead integrates molecular findings with gross, microscopic, and clinical findings.