The etiology of cancer is very complex and yet to understand thoroughly. One of the most complex type of them is pancreatic cancer, especially Pancreatic Adenocarcinoma which is also the most common form of pancreatic cancer. Researchers have shown that specific gene mutations are the initial footstep of this form of can-cer, for example inactivation of tumor-suppressor genes such as p16, DPC4, and p53, or activation of oncogenes such as K-ras, are a few of the mutations that trigger the growth of Pancreatic Adenocarcinoma. Althoughthere could be many other aspects of molecular crosstalk that can help in promotion and progression of it. miRNAs and Epigenetic modifications also play an important role in the progression of pancreatic cancer. Several tumor suppressor genes can be silenced due to hypermethylation of CpG island in promoter region. Other studies indicate the involvement of miRNAs in the regulation of cell proliferation and apoptosis, as well as their altered expression in pancreatic can-cer. This review tried to give an overlook on the molecular pathogenesis of pancreatic adenocarcinoma at different level of molecular interactions.