To elucidate the epigenetic landscape of Schwann cell tumors, DNA methylation profiling was performed on histological schwannomas (n = 67), plexiform neurofibromas from patients with clinical diagnoses of NF-1 (n = 10), or MPNSTs (n = 42), all from patients who were treated at a single institution from 1991 to 2021. This evidence concerns the gene NF1 and plexiform neurofibroma.