Lyskjær I, Lindsay D, Tirabosco R, et al. - This study was intended to present histone 3 lysine 27 trimethylation (H3K27me3) expression and methylation status in histological variants of malignant peripheral nerve sheath tumours. Researchers illustrate that overall in 38% of MPNSTs, loss of H3K27me3 expression occurs, but is lost in 76% of histologically classical cases, whereas loss was diagnosed in only 23% cases with heterologous elements and 14% where the diagnosis could not be provided on morphology alone. In MeGroups 4 and 5, the methylation profiles of MPNSTs with retention of H3K27me3 are independent of mutations in PRC2 core components and the driver(s) in these groups remain to be distinguished. The data open new avenues of evaluation.