Carcinogenesis is a multi-aetiological process involving alterations of key biomolecular markers. These are recognised by the humoral system and known as Tumour Associated Antigens (TAA) against which the humoral system mounts an auto-antibody response. Cancer cells are subject to two key mortality barriers (M1 & M2) as described in the “2-hit” hypothesis. These are overcome by p53 dysfunction in M1 and hTERT re-expression in M2. Auto-antibodies are produced in response to these two TAA. This book investigates the significance of the anti-p53 and anti-hTERT auto-antibody response. The initial literature review of anti-p53 auto-antibody in all cancers (1979-2010) forms the largest body of evidence of correlation between anti-p53 auto-antibody and p53 mutation to date. This is followed by results of our anti-p53 study and evaluation of all published studies of anti-p53 in colorectal cancer. Anti-hTERT has only been reported once, using molecular recombination to develop the hTERT antigen. The latter section of this book aims to develop a less restrictive technology for mass detection of anti-hTERT. This humoral response could enable earlier identification of CRC and impact prognosis.