Abstract: Objective To investigate the etiology, diagnosis and treatment options of simultaneous multiple myeloma and colon cancer. Methods The clinical data of 1 case of the multiple myeloma and colon cancer patient with secondary liver metastasis were retrospectively analyzed, and the relevant literature was reviewed. Results Anemia was the first symptom of the patient, and multiple myeloma was indicated by bone marrow aspiration. The positive of 14q32 IgH gene rearrangement was revealed by fluorescence in situ hybridization, the colon cancer was diagnosed by colonoscopy and pathological biopsy, and the space occupying liver lesion was found a few months later. The colon cancer resection surgery was performed after VTD regime relieved the bone marrow load, then VTD and XELOX combined chemotherapy was performed postoperatively, and local radiofrequency ablation of liver lesions was performed for liver occupying space, the patient could tolerate it, and the liver metastases were significantly smaller than before. Conclusion Simultaneous multiple myeloma and colon cancer with liver metastasis are rare, the histopathology examination is necessary for differential diagnosis of primary and metastatic carcinoma, the treatment of which has not been standardized, the therapeutic plan need to be developed by the multidisciplinary assessment.