Multiple myeloma is characterized by the accumulation of clonal, malignant plasma cells in the bone marrow. Multiple lytic skeletal lesions in some tumor patients with multiple myeloma are easily considered as bone metastases secondary to tumors, resulting in a missed diagnosis of multiple myeloma. Herein, we report a rare case, in which rectal cancer with multiple myeloma was initially misdiagnosed with bone metastases secondary to rectal cancer, due to the symptoms of multiple lytic sketetal lesions, and ignoring the abnormal plasma cells in the peripheral circulating blood smear. The patient was finally diagnosed with coexistence of rectal cancer and multiple myeloma. The case focuses on the importance of the peripheral circulating blood smear detection.