In this study, we investigated whether the serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in gemcitabine resistance and the maintenance of pancreatic cancer stem cells (CSCs) in association with an Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator of transcription. This evidence concerns the gene EZH2 and pancreatic neoplasm.