The cancer invasion of the large intestine, a destructive process that begins within the mucous membrane, causes cancer cells to gradually erode specific layers of the intestinal wall. The normal tissues of the intestine are progressively replaced by a tumour mass, leading to the impairment of the large intestine’s proper morphology and function. At the ultrastructural level, the disintegration of the extracellular matrix (ECM) by cancer cells triggers the activation of inflammatory cells (macrophages) and connective tissue cells (myofibroblasts) in this area. This accumulation and the functional interactions between these cells form the tumour microenvironment (TM). The constant modulation of cancer cells and cancer-associated fibroblasts (CAFs) creates a specific milieu akin to non-healing wounds, which induces colon cancer cell proliferation and promotes their survival. This review focuses on the processes occurring at the “front of cancer invasion”, with a particular focus on the role of the desmoplastic reaction in neoplasm development. It then correlates the findings from the microscopic observation of the cancer’s ultrastructure with the potential of modern radiological imaging, such as computer tomography (CT) and magnetic resonance imaging (MRI), which visualizes the tumour, its boundaries, and the tissue reactions in the large intestine.