Amphicrine carcinomas are rare tumors defined by the presence of tumor cells showing evidence of both exocrine and endocrine differentiation. We here report two cases of amphicrine carcinomas of the pancreas, an exceedingly rare localization for this type of tumors. Diagnosis was made in respectively, a 32-year-old woman and a 66-year-old man; tumors measured 7 and 3 cm in diameter; metastatic dissemination was present in both cases. The first patient, treated by surgery and chemotherapy, is alive, without disease progression, after 26 months; the second patient deceased early after the diagnosis. In both cases, the first diagnosis considered at cytological and histological examination was endocrine carcinoma. The amphicrine nature of the lesion was ascertained by the combined demonstration of mucus staining and chromogranin A expression in the same cells. In one case, the amphicrine nature of tumor cells was confirmed by the ultrastructural examination. The identification of the amphicrine nature of an apparently endocrine tumor is of relevance, because of the poor prognosis of amphicrine carcinomas as compared to endocrine carcinomas and the requirement for aggressive therapy.