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Objective To investigate the clinical features of several cases of malignancy with multiple bone lesions as the first manifestation. Methods Forty-nine cases of malignancy with multiple bone lesions as the first manifestation were retrospectively analyzed from May 2018 to July 2019. All patients complained of “pain at the site of bone lesion” upon admission. Baseline patient information, such as age, gender, location of bone lesions, etiology, diagnosis method, time of onset was collected. Results The median age of the patients was 56 years old, of which 83.7％ (41/49) were aged ≥50 years. The median time of onset was 2 months. Among the cases, 40 were confirmed as solid tumor bone metastasis, whereas the remaining 9 cases as hematological system tumor. Lung cancer and multiple myeloma were the main tumor types, accounting for 40.8％ (20/49) and 16.3％ (8/49), respectively. Other common causes were seven cases of cancer affecting the digestive system (three cases of liver cancer, three cases of gastric cancer, and one case of esophageal cancer), as well as seven cases of unknown primary cancer. Half of the solid tumors had only multiple bone metastases but no other distant metastasis. Conclusion Multiple bone lesions accompanied by pain may be the first clinical manifestation in various malignant tumors. The common tumor types were lung cancer, multiple myeloma, and digestive system tumor. It is more common in people aged 50 years and older. Multiple bone lesions might be the only metastasis site of some solid tumors, and its mechanism needs further investigation.