The ability of Medicine to effectively treat and cure cancer is directly dependent on their capability to detect cancers at their earliest stages. The advent of proteomics has brought with it the hope of discovering novel biomarkers in the early phases of tumorigenesis that can be used to diagnose diseases, predict susceptibility, and monitor progression. This discipline incorporates technologies that can be applied to complex biosystems such as serum and tissue in order to characterize the content of, and changes in, the proteome induced by physiological changes, benign or pathologic. These tools include 2-DE, 2D-DIGE, ICAT, protein arrays, MudPIT and mass spectrometries including SELDI-TOF. The application of these tools has assisted to uncover molecular mechanisms associated with cancer at the global level and may lead to new diagnostic tests and improvements in therapeutics. In this review these approaches are evaluated in the context of their contribution to cancer biomarker discovery. Particular attention is paid to the promising contribution of the ProteinChip/SELDI-TOF platform as a revolutionary approach in proteomic patterns analysis that can be applied at the bedside for discovering protein profiles that distinguish disease and disease-free states with high sensitivity and specificity. Understanding the basic concepts and tools used will illustrate how best to apply these technologies for patient benefit for the early cancer detection and improved patient care.