Colorectal cancer (CRC) is the second most prevalent cancer in Australia, with over 4000 deaths annually and worldwide approximately 600,000 deaths with an annual incidence of a 1.2 million cases. Despite potential curative surgery, over 50% of CRC patients develop recurrent or metastatic disease where the 5 year survival rate is less than 10%. Currently the only widely used non-invasive screening test for CRC is the faecal occult blood test (FOBT). Even though screening with FOBT has been shown to lead to reductions in CRC incidence and mortality, there are significant issues that limit its effectiveness as a diagnostic screening tool, such as a poor positive predictive value of 5.3% for suspected cancer and low participation rate of approximately 40% in the National Bowel Cancer Screening Program. To overcome some of the limitations of the FOBT, we believe that a blood test may increase participation rates and could provide a useful adjunct to FOBT. Presently, we have therefore analysed over 55 protein biomarkers in 4 independent cohorts of CRC patients (Dukes stages A-D) compared against age and gender matched healthy controls. Using logistic regression, we have identified a panel of biomarkers in serum with a predictive sensitivity of 71% and a specificity of 95% that could be used for the diagnosis and early detection of CRC when surgery and therapy are most likely to be effective.