We used polarization spectroscopy to investigated changes in subepithelial blood supply in the initial stages of colon carcinogenesis. We observed, for the first time, a profound early increase in subepithelial blood supply (EIBS) at a time point that precedes the development of adenomas as well as any other currently available markers of colon cancer. Although it has been previously established that later-stage lesions (e.g. at the adenoma-carcinoma stage) have increased blood supply, ours were the first data to show such early aberrations of blood supply in early predysplastic stages of colon carcinogenesis. Therefore, optically detectable EIBS may potentially be used for diagnosis of previously undetectable stages of colonic neoplasia and may provide further insights into the pathophysiology of the earliest stages of colon carcinogenesis.