Introduction: Central Nervous System (CNS) Solitary Fibrous Tumor (SFT) / Hemangiopericytoma (HPC) is a fibroblastic mesenchymal tumor of the meninges that accounts for < 1% of intracranial tumours. The natural history of CNS SFT / HPC is characterized by a high rate of local (60%) and distant (20%) failure following gross total resection (GTR), and treatment options are limited. The identification of new genomic markers could be of interest to improve the understanding and management of CNS SFT / HPC. We present the results of a search for molecular alterations by next-generation sequencing (NGS) in a patient diagnosed with CNS SFT / HPC who experienced rapid distant failure. Case Description: A 64-year-old Caucasian man was diagnosed with a right hemisphere extra-axial frontal tumor after being referred for persistent headaches in October 2017. The patient underwent surgical resection followed by adjuvant radiation therapy of the operative cavity. A diagnosis of grade III HPC of the CNS was established. A diffuse metastatic recurrence with multiple bone lesions occurred rapidly after the initiation of radiation therapy. In July 2018, a CT-guided biopsy of the left iliac crest confirmed a highly proliferative metastatic recurrence and a FoundationOne CDx TM test was performed, which showed a somatic mutation of the tumor suppressor gene TP53 (Tumor Protein p53) (R175H). The microsatellite status was stable and the Tumor Mutational Burden (TMB) was low (1 Muts/Mb). A massive disease evolution of the disease occurred in September 2018. The patient died in November 2018 after neurological decline. Conclusion: This case report shows that an anatomopathological examination alone is insufficient to correctly classify these rare tumors and predict their aggressiveness. In this case report, the somatic mutation of TP53 (R175H) was associated with a very poor prognosis (survival of 13 months). Further studies including systematic NGS of CNS SFT / HPC are warranted to investigate the role of TP53 in prognostic assessment to adapt future treatment strategies.