Colorectal cancer is one of the most prevalent malignant tumors in China. Chemotherapy, targeted therapy, and immunotherapy constitute the primary treatment modalities for patients with metastatic colorectal cancer. With the advancement of precision medicine, next-generation gene sequencing has become an essential component of the diagnostic and therapeutic process for metastatic colorectal cancer. Gene sequencing results provide critical guidance for the formulation of individualized treatment strategies. However, colorectal cancer exhibits significant tumor heterogeneity. Within the same patient, genetic profiles may differ between primary and metastatic tumors, as well as between tumor tissues obtained before and after treatment. A comprehensive and accurate understanding of these genetic differences is crucial for optimizing treatment efficacy. To address this issue, the Multidisciplinary Diagnosis and Treatment Committee of the Guangdong Anti-Cancer Association convened a panel of domestic multidisciplinary experts to develop the Expert Consensus on Genetic Testing for Patients with Metastatic Colorectal Cancer Based on Tumor Heterogeneity (2025 Edition) following extensive discussions. This consensus aims to maximize patient treatment outcomes and enhance the overall standard of colorectal cancer diagnosis and management in China.