Diagnosing central nervous system (CNS) tumours post-radiation therapy is often complicated by treatment-induced histological changes. Molecular diagnostics, such as methylation profiling, offer robust tools to aid in accurate tumour classification. The present study reported a case of a 48-year-old woman with a recurrent parasellar mass previously treated with stereotactic radiosurgery. Despite imaging suggestive of meningioma, histopathology and immunohistochemistry yielded ambiguous findings. Low-coverage whole genome methylation profiling using Oxford Nanopore sequencing provided a conclusive diagnosis of meningioma, with a classifier confidence score of 0.791, supported by t-distributed stochastic neighbor embedding clustering and characteristic copy number variations. The present case illustrated the diagnostic utility of methylation profiling in post-treatment CNS tumours with perplexing histopathology. Integration of molecular diagnostics can enhance classification accuracy and inform clinical decision-making. © 2025 Handoko et al.