Our findings advocate a refined diagnostic protocol: RNA-based next-generation sequencing (RNA-NGS) must be prioritized in STAT6-immunopositive central nervous system (CNS) mesenchymal tumors when DNA-NGS fails to identify the pathognomonic NAB2::STAT6 fusion, as demonstrated by the resolution of diagnostic ambiguity through detection of a cryptic NAB2-exon4::STAT6-UTR fusion in this case. Here, NAB2 is linked to mesenchymal cell neoplasm.