Purpose: To elucidate the actual state of difficulties and related factors of nurses in caring for patients with recurrent and metastatic malignant musculoskeletal tumor. Methods: The subjects were 315 nurses from 12 institutions that treat malignant musculoskeletal tumor. We researched the difficulties of nurses regarding cancer nursing and care of patients with malignant musculoskeletal tumor. We examined the related factors by multiple regression analysis. Result: 165 nurses responded (effective response rate 52.4%). Among “Nurses’ difficulty with cancer care”, the level of difficulty regarding communication was the highest and in own knowledge/technology, system/regional cooperation was also high. Among “Nurses’ difficulty with care for patients with malignant musculoskeletal tumor”, there was a high degree of difficulties regarding the target characteristics of care. Related factors were facility characteristics, nursing experience, nursing experience of musculoskeletal tumor, learning methods for musculoskeletal tumor nursing, and multi-professional conferences. Conclusion: Nurses caring for patients with malignant musculoskeletal tumor have specific difficulty due to total pain, age of onset, and rarity. Educational support based on related factors is therefore required.