Despite a modern validated regimen of chemotherapy, advanced pancreatic adenocarcinoma remains the fourth most common cause of cancer-related death worldwide. The phosphoinositide 3-kinase pathway (PI3K)/Akt/mammalian target of rapamycin (mTOR) is a major signaling pathway that may be activated in advanced pancreatic cancer. To highlight the potential interest of this targetable pathway in selected advanced pancreatic cancer patients, we report herein a patient with an activated PI3K mutation who was treated in a phase I trial evaluating a treatment combination including an mTOR inhibitor.