Pancreatic cancer is the fourth most common cause of cancer death in Western society and is a leading cause of cancer death worldwide. Its incidence and mortality rates are almost identical. Surgery is the only treatment theoretically curative, but < 20% of all patients admitted with ductal adenocarcinoma of the pancreas undergo resection and at best, 25% of those survive for 5 years. The identification of prognostic factors that are able to stratify patient populations recognizing those that could able to benefit by a radical surgical treatment and/or a chemotherapeutic treatment. This paper is a not only a detailed review of existing studies evaluating pancreatic cancer biomarkers, but also a critical evaluation of the real clinical use of these kinds of prognostic factors with the purpose to help discriminate between a variety of factors which, so far, can be considered really useful in everyday clinical practice. Although no single marker has been shown to be perfect in predicting patient outcome, a profile based on the best of these markers may prove useful in directing patient therapy. The markers with the strongest evidence as independent predictors of patient outcome include, p16, MMP7 and vascular endothelial growth factor.