Extracranial metastasis of glioblastoma (GBM) is an extremely rare phenomenon and is associated with a poor prognosis. Here, we present the case of a 55-year-old woman who developed pleural metastasis of GBM, manifesting non-specific breathing difficulties during treatment. This case highlights the importance of integrating multiple diagnostic approaches, as only the comparison of histopathological examination results with the patient’s clinical history – right temporal lobe GBM – enabled the final diagnosis of GBM metastasis. Next-generation sequencing was performed as part of the diagnostic workup and revealed a p.G266R TP53 mutation. Additionally, imaging revealed an extensive heterogeneous lesion at the site of the previously resected GBM, which proved to be an inoperable gliosarcoma (World Health Organization grade 4). This rare presentation of GBM with distant pleural metastasis, combined with the identification of an uncommon TP53 mutation, represents a unique diagnostic and clinical challenge and underscores the novelty of this case.