Aspergillus spp. are widespread environmental pathogens that can induce invasive aspergillosis, especially in immunocompromised patients. An 86-year-old female patient presented with a rare case of invasive cerebral aspergillosis. The aspergilloma invaded the intracranial region originating from the ethmoidal sinus and the orbital apex. In contrast to routine diagnostic procedures, next-generation sequencing (NGS) was able to identify the fungal pathogen in the cerebrospinal fluid as well as in plasma samples, supporting the biopsy-based diagnosis of invasive cerebral aspergillosis. Therefore, NGS-based diagnostics may be of particular importance for difficult-to-diagnose disease states, when conventional diagnostic procedures fail.