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Low-grade myofibroblastic sarcoma (LGMS) is a rare, indolent mesenchymal neoplasm exhibiting myofibroblastic differentiation, with a propensity for local recurrence. The molecular basis of LGMS and its precise relationship with other histologic mimics have remained largely undefined. To address this gap, we conducted the first comprehensive multiomics analysis of six LGMS cases, integrating whole-exome sequencing (WES), RNA sequencing, and Illumina MethylationEPIC v2 array profiling, with comparative analysis against public sarcoma methylation cohorts and related fibroblastic tumors. Clinically, patients (median age 35.5 years) presented with small tumors (median 1.45 cm), predominantly located in the head and neck, displaying classic histologic features of diffusely infiltrative spindle cell fascicles with patchy mononuclear inflammation. Two of five patients with follow-up developed local recurrence, and none metastasized (median follow-up 92.5 months). Genomically, all LGMS exhibited low tumor mutational burden (median 2.31 mut/Mb) and minimal fraction of genome altered, with TP53 and TSC2 deletions and NTRK1 and ERBB3 amplifications found in a subset of cases. No pathogenic fusions were detected. Transcriptomic profiling revealed a distinct signature featuring prominent USP6 overexpression and upregulation of inflammatory and immune-related genes, including CD274 (PD-L1), and enrichment of inflammatory and interferon-γ response signatures. Epigenetically, LGMS formed a unique methylation cluster closest to inflammatory myofibroblastic tumor, with numerous differentially methylated regions and higher immune infiltration, particularly monocytes, compared with other fibroblastic tumors. These findings establish LGMS as a genomically stable, epigenetically distinct myofibroblastic sarcoma driven by USP6 overexpression and an inflammation-enriched transcriptome. They support its recognition as a standalone entity, facilitate integration into methylation-based sarcoma classifiers for improved diagnostic precision, and nominate USP6-associated pathways and immune checkpoint blockade as promising therapeutic strategies for recurrent or unresectable disease.