Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide. Histopathological evaluation remains the cornerstone of diagnosis, while immunohistochemical biomarkers increasingly contribute to prognostic assessment and therapeutic decision-making. Ki-67 is a well-established nuclear proliferation marker expressed during the active phases of the cell cycle and has been extensively investigated as an indicator of tumor growth and biological aggressiveness. Conventional visual estimation of Ki-67 labeling index is subject to considerable interobserver variability, leading to growing interest in quantitative digital image analysis. Modern image analysis platforms enable automated detection of positively stained nuclei, objective calculation of proliferation indices, improved reproducibility, and integration with artificial intelligence-based diagnostic systems. This review summarizes the biological significance of Ki-67, current immunohistochemical assessment methods, principles of quantitative image analysis, clinical applications in colorectal cancer, limitations, and emerging developments in digital pathology. Published evidence indicates that quantitative image analysis offers greater standardization and precision than manual assessment and has the potential to improve prognostic evaluation when combined with clinicopathological parameters and molecular biomarkers.