Pancreatic acinar cell carcinoma (ACC) is a rare, malignant epithelial neoplasm. SALL4 is a zinc-finger transcription factor and a member of the SALL gene family that has been previously expressed in numerous malignancies including breast, lung, colorectal, and hepatocellular carcinomas but not in pancreatic adenocarcinoma. The expression of SALL4 is related to early clinical stage in breast and lung carcinomas but with early metastasis and an unfavorable prognosis in liver and colorectal carcinomas. In this study, we report two ACC cases with SALL4 expression. Interestingly, one of these two cases also had elevated alpha-fetoprotein (AFP) while both cases showed neuroendocrine features. Clinically, these two patients responded very well to chemotherapy, and the second patient is alive without recurrence and metastasis for more than four years. To our knowledge, these are the first reported cases of SALL4 expression in pancreatic acinar cell carcinoma, indicating a role of SALL4 in this tumor.