The aim of this study was to investigate the ultrastructural appearance of mirror biopsies from primary colorectal adenocarcinomas combined with serotonin, vasoactive intestinal polypeptide, bombesin, somatostatin and glucagon expression in order to clarify the histology and immunology of these tissues compared with colorectal adenocarcinomas. The investigation was carried out in 90 cases of mirror biopsies by electron microscope immunocytochemistry. The ultrastructural study revealed that some cases (30%) of mirror biopsies were characterized by the presence of intracellular changes compared to normal tissues. The most significant of them were the presence of swollen abnormal mitochondria and the increased number of the secretory cells. The above enzymic and secretory changes were confirmed by electron immunogold results. Bombesin and VIP appeared to be located in enterochromaffin-like (ECL) endocrine cells primarily responsible for the production of serotonin. Somatostatin was located in D cells while we found numerous glucagon (EG) immunoreactive cells. In conclusion, low somatostatin expression, high glucagon and serotonin expression and the ectopic secretion of VIP and bombesin neuropeptides in mirror biopsies indicate the preneoplastic nature of these tissues and may be useful for the optimal treatment of patients with colorectal adenocarcinoma.