Colorectal cancer (CRC) is still a major killer, mainly due to the lack of early detection biomarker with sensitivity/specificity. Conventional histopathology is the gold standard approach in practice, but there are still some issues (false diagnosis and long waiting period). Aggregation-induced emission (AIE) is a novel photophysical phenomenon which has been widely utilized for biological imaging in vivo, including malignant cells, showing remarkable imaging contrast and enhanced emission in high concentrated state. However, it is unclear if AIE dyes can identify malignant cells specifically in vivo. A great challenge for specific labeling of malignant cells is probably ascribed to the complex compositions in tumor tissues. Herein, an AIE dye-based mitochondria-targeted histological staining strategy was employed to localize cancer and the metastatic track in the fresh colorectal cancer. This novel approach holds great potential to revolutionize the clinical diagnosis and intervention for devastating malignancy.