In this study, we describe, compare, and discuss several subcellular alterations found in Colorectal Adenocarcinoma and peritumoral tissue using transmission electron microscopy, morphometry, and statistical analysis. Tissue samples from anterior resections were collected from patients diagnosed with Colorectal Adenocarcinoma in the University Hospital of Caracas. Samples were processed according to the typical protocol for their observation through transmission electron microscopy. The resulting images were analyzed using specialized software for the collection of morphometric data. Several anomalies were common for both tissues, including but not limited to, rough endoplasmic reticulum and mitochondrial swelling, nuclear invagination, nuclear enlargement, and cellular swelling. In general, alterations within the tumor were more frequent and intense. Extensive organellar degradation and other evidences of cellular damage seemed to extend past the edge of the tumor into the peritumoral tissue. There seems to be a clear process of lateral cancerization present in the peritumoral area. The tissue layers composed of smooth muscle cells, probably due to their structural features, may allow greater diffusion of harmful substances produced by the tumor. A more in-depth analysis of peritumoral tissue considering organellar damage and morphometric data may provide relevant insight about the changing microenvironment promoted by the close proximity of a tumor.