The aim of this study was to investigate serotonin and bombesin expression in colorectal adenocarcinomas and neuroendocrine colorectal tumors to clarify their role in the progression of colon cancer. The investigation was carried out by electron microscope immunocytochemistry. The ultrastructural study revealed that some cases of colorectal adenocarcinomas were characterized by the presence of amphicrine cells containing endocrine granules and mucus granules. Poorly differentiated adenocarcinomas and liver metastases were poorly granulated compared with highly differentiated tumors. Neuroendocrine tumors nevertheless were characterized by the presence of numerous malignant neuroendocrine cells filled with secretory granules and mucus granules. Bombesin appeared to be located in enterochromaffin-like endocrine cells, which are primarily responsible for the production of serotonin. In colorectal adenocarcinomas there was an inverse correlation between serotonin levels and the degree of differentiation. High serotonin levels characterized colorectal adenocarcinomas with composite phenotype and colorectal neuroendocrine tumors. Increased bombesin expression was correlated with colorectal adenocarcinomas exhibiting poor histological grade and their liver metastases. In conclusion, the findings suggest that high serotonin levels may be an indicator of neuroendocrine differentiation, and bombesin may be a useful marker for colorectal adenocarcinomas with aggressive behavior.