Background and objectives: The epithelial and stromal tissues both play a role in the progression of colorectal cancer (CRC). The aim of this study was to assess the expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax in the epithelium as well as the lamina propria of normal colonic controls, low-grade tumor samples and high-grade tumor samples. Materials and Methods: A total of 60 samples consisting of both normal colonic and carcinoma samples was collected from the Department of Pathology, Cytology and Forensic Medicine, University Hospital Center, Split from January 2020 to December 2021. The expression of Bcl-2 and Bax markers was semi-quantitatively and quantitatively evaluated by recording immunofluorescence stain intensity and by counting stained cells in the lamina propria and epithelium. Analysis of positive cells was performed using the Mann-Whitney test. Results: In all samples, Bcl-2 was significantly more expressed in the lamina propria when compared with the epithelium. Bax was significantly more expressed in the epithelium of normal and low-grade cancer samples when compared with their respective laminae propriae. The percentage of Bcl-2-positive cells in lamina propria is about two times lower in high-grade CRC and about three times lower in low-grade CRC in comparison with healthy controls. Contrary to this, the percentage of Bax-positive cells was greater in the epithelium of low-grade CRC in comparison with healthy control and high-grade CRC. Conclusions: Our study provides a new insight into Bcl-2 and Bax expression pattern in CRC. Evaluation of Bcl-2 expression in the lamina propria and Bax expression in the epithelium could provide important information for colorectal cancer prognosis as well as potential treatment strategies.