Malignant fibrous histiocytoma of the bone (MFH-B) is an extremely rare and aggressive malignancy. The clinicopathological characteristics and prognosis of patients with MFH-B have not been defined. We conducted a retrospective study using the data of all MFH-B patients from the Surveillance, Epidemiology and End Results (SEER) database between 1975 and 2016. Initially, the clinicopathological characteristics were described. The difference in prognosis between patients with MFH-B and those with osteosarcoma was compared using propensity score matching analysis. Then, the features affecting the prognosis of patients with MFH-B were further determined using Cox regression analysis. A total of 318 patients with MFH-B were identified. The median overall survival (mOS) of all 318 patients with MFH-B was 29.0 months. The 1-, 3-, 5-, and 10- year survival rates were 67.4%, 53.6%, 38.7%, and 28.7%, respectively. The multivariate Cox regression analysis showed that older age, distant metastases, and flat bone lesion were independent factors for worse prognosis, whereas surgery was an independent factor for favorable survival, and this intervention could decrease risk of death by 61% (HR = 0.39, 95% CI 0.28-0.54). Apart from this, the prognosis of patients with MFH-B was significantly worse than that of patients with osteosarcoma in both unmatched and matched cohorts. In conclusion, MFH-B is a rare malignant bone cancer, with relatively worse prognosis than osteosarcoma. Older age, distant metastases, flat bone lesion, and surgery were independently associated with prognosis. In order to understand this disease more thoroughly and accurately, more cases with adequate information are required in the future.