We herein present the case report of a 83-year-old female patient who had undergone right colon resection for adenocarcinoma 2 years earlier, and developed osteolytic lesions of the right femur 6 months ago. A roentgenogram of the right thigh, technetium-99m phosphate bone scintigraphy and combined 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography imaging were performed, and the results revealed multiple osteolytic lesions in the humerus bilaterally, the right scapula and the right femur. The lesions were suspected to be colon cancer metastases. To improve the quality of life of the patient, palliative surgery was performed. However, the intraoperative biopsy of the focal lesions and immunohistochemical evaluation revealed multiple myeloma (MM). Chemotherapy was administered 2 weeks after surgery and the patient recovered uneventfully. The manifestations of MM and bone metastases are occasionally similar. Although the coexistence of the two diseases is rare, both conditions should be considered in the differential diagnosis of osteolytic lesions.