Current understanding of colorectal carcinogenesis suggests a series of genetic changes occurring pari passu with morphological changes ultimately resulting in a cancerous lesion. The adenomatous polyp was originally the prototype of the preneoplastic lesion but recently, other colonic polyps, primarily the hamartomas, have been clinically characterized as colorectal cancer biomarkers with genetic changes found mainly in the mesenchymal component as opposed to the ectodermal, or epithelial element. This, with the current interest in angiogenesis playing a role in the propagation of neoplastic lesions, has now encompassed every tissue element and opened the way for an understanding of the oncogenic process. This has suggested that considerable interaction occurs between all tissue elements, including what was previously described as epithelial-matrix interactions. While hyperplastic polyps are thought not to confer risk for cancer, they may offer clues as to the first steps of the overall process. Microadenomas have introduced new clinical as well as biological considerations, as unique risk factors. Investigation of these lesions has moved from purely morphological correlations to mechanistic dissections of important biological pathways using both genetic and protein chemistry tools. This review explores the microcosm of the colonic polyp and its relation to cancer as the quintessential premalignant biomarker.