Pancreatic adenocarcinoma accounts for nearly 90-95% of exocrine malignant tumors of the pancreas. Traditionally, overexpressed proteins/epitopes such as CA 19-9, CA-50, CEA, and many others were being used as pancreatic cancer tumor markers. The main utility of these biomarkers was in the diagnosis of pancreatic cancer as well as to assess response to chemotherapy and to determine prognosis and to predict tumor recurrence. However, these markers had significant limitations such as lack of sensitivity, false-negative results in certain blood groups, as well as false-positive elevation in the presence of obstructive jaundice. To circumvent these limitations, an extraordinary amount of research is being performed to identify an accurate tumor marker or a panel of markers that could aid in the management of the pancreatic cancer. Although this research has identified a large number and different variety of biomarkers, few hold future promise as a preferred marker for pancreatic cancer. This review provides an insight into exciting new areas of pancreatic biomarker research such as salivary, pancreatic juice, and stool markers that can be used as a noninvasive test to identify pancreatic cancer. This manuscript also provides a discussion on newer biomarkers, the role of microRNAs, and pancreatic cancer proteomics, which have the potential to identify a preferred tumor marker for pancreatic adenocarcinoma. This review further elaborates on important genetic changes associated with the development and progression of pancreatic cancer that holds the key for the identification of a sensitive biomarker and which could also serve as a therapeutic target.