Colorectal cancer (CRC) is one of the most prevalent cancers of both genders on a global scale. While newer surgical techniques and improved radio-chemotherapy regimens have improved survival over the past decades, still, almost 50% of patients eventually develop recurrent disease and metastasis and die within 5 years of diagnosis. Improved understanding of the colorectal carcinogenesis will hopefully yield new ways of early detection and diagnosis, cancer prevention, and targeted therapies. The genomic and proteomic understanding of CRC continue to evolve at the molecular level. Knowledge has evolved from the perceptions of cancer in ancient times, to the development of the “adenomacarcinoma model“ to the current molecular classification of CRC as a genetic disease involving instability at the chromosomal, epigenetic and microsatellite level of the DNA. Further, the dimensions of cancer development now include not only the hallmarks of the cancer cell, but stem cell theories, colorectal crypt formation theories on adenoma development and, a complex interaction with the extracellular matrix (ECM) and its cellular components (immune system, cell signaling, connective tissue). This review aims to give an abbreviated yet concise overview of the current multidimensional understanding of the molecular genesis in colorectal carcinogenesis.