Updated publication reference for PubMed record(s): 25624350. Unbiased proteomic analysis of plasma samples holds the promise to reveal clinically invaluable disease biomarkers. However the tremendous dynamic range of the plasma proteome has so far hampered the identification of such low abundant markers. To overcome this challenge we analyzed the plasma microparticle proteome, and reached an unprecedented depth of over 3,000 plasma proteins in single runs. To add a quantitative dimension, we developed PROMIS-Quan – PROteomics of MIcroparticles with Super-SILAC Quantification, a novel mass spectrometry-based technology for plasma microparticle proteome quantification. PROMIS-Quan enables a two-step relative and absolute SILAC quantification. First, plasma microparticle proteomes are quantified relative to a super-SILAC mix composed of cell lines from distinct origins. Next, the absolute amounts of selected proteins of interest are quantified relative to the super-SILAC mix. We applied PROMIS-Quan to prostate cancer and compared plasma microparticle samples of healthy individuals and prostate cancer patients. We identified in total 5,374 plasma-microparticle proteins, and revealed a predictive signature of 3 proteins that were elevated in the patient-derived plasma microparticles. Finally, PROMIS-Quan enabled determination of the absolute quantitative changes in prostate specific antigen (PSA) upon treatment. We propose PROMIS-Quan as an innovative platform for biomarker discovery, validation and quantification in both the biomedical research and in the clinical worlds.