Pancreatic cancer is a devastating disease, with a mortality rate almost identical with its incidence. Late diagnosis and limited therapeutic options make early detection of pancreatic cancer a pressing clinical problem. In this context, the investigation of the pancreatic cancer proteome has recently gained considerable attention because profiles of proteins may be able to more accurately identify disease states, such as cancer. Recent pancreatic cancer proteome studies may be categorized into basic studies cataloguing the pancreatic proteome, studies investigating differential protein expression patterns, and studies searching for proteome-based biomarkers for early cancer detection and differentiation. Although these studies clearly demonstrate that a range of biological samples are suitable for proteomic analyses, comparison of different studies is problematic due to the diversity of methodologies, sample sources, and characterization of patient populations. Reproducibility between studies has rarely been investigated, and no investigation has compared the different methods of proteomic research. The results of this review have shown that more stringent requirements concerning the design and the analysis of future studies should be implemented. These include an adequate patient number, obligatory histological examination of tissues, appropriate control groups, identification of proteins and peaks, validation of differential expression using independent cohorts and/or a second methodology, and, finally, demonstration of result reproducibility. This will hopefully lead to the discovery of prognostic and predictive biomarkers that help to improve prognosis of pancreatic cancer patients.