The current methods widely deployed for colorectal cancer (CRC) screening are grossly inadequate on sensitivity and specificity ground. Cancer specific biomarkers are found in low concentrations (pg- ng/mL) in plasma as a result of structural changes in the microenvironment of cancer tissues followed by dilution in plasma. This study was designed to meet the longstanding unmet clinical need for cancer screening and surveillance using minimally invasive techniques. Expression of 92 potential biomarkers were measured from clinically stage CRC (Duke’s A, B, C, D) and control (i.e., unaffected) EDTA plasma samples utilizing PEA based Proseek® Multiplex Oncology I kit. A duplicate set of samples were analysed by Bio-Plex Pro™ human cytokine 27-plex immunoassay kit. Expression of CEA (a diagnostic biomarker for CRC) was found to be significantly high in malignant stage while IL 8 and prolactin had significant level of expression between control, benign and malignant stages. Additional experiments are being conducted on the same set of plasma using commercially available MARS 14 followed by in house immune based depletion system. The aim is to detect low abundance novel biomarkers using state-of-the-art LC-MS instrumentation housed in Australian Proteome Analysis Facility. In addition, uHPLC based analysis is being conducted on these samples to identify any fluctuation trend in kynurenine pathway in various cancer stage. The outcomes from this study will be followed up with a subsequent investigation where expression of 17 new proteins will be measured by PEA technology as well as statistical correlation will be established between the expression and clinical data. We believe these findings will enable to establish new, improved and volume-sparing plasma biomarkers/biomarker signature panels. The detailed results will be presented at the upcoming Lorne Proteomics conference which would specifically provide useful information to researchers about a longstanding unmet clinical need for early stage CRC detection.