AbstractMyxoinflammatory fibroblastic sarcoma (MIFS) has recurrent genetic features in the form of a translocation t(1;10)(p22‐31;q24‐25),BRAFgene fusions, and/or an amplicon in 3p11‐12 including theVGLL3gene. The breakpoints on chromosomes 1 and 10 in the t(1;10) cluster in or near theTGFBR3andOGAgenes, respectively. We here used a combination of deep sequencing of the genome (WGS), captured sequences (Cap‐seq), and transcriptome (RNA‐seq) and genomic arrays to investigate the molecular outcome of the t(1;10) and theVGLL3amplicon, as well as to assess the spectrum of other recurrent genomic features in MIFS. Apart from aROBO1‐BRAFchimera in a t(1;10)‐negative MIFS‐like tumor, no fusion gene was found at RNA‐seq. This was in line with WGS and Cap‐seq results, revealing variable breakpoints in chromosomes 1 and 10 and genomic breakpoints that should not yield functional fusion transcripts. The most common genomic rearrangements were breakpoints in or around theOGA,NPM3, andFGF8genes in chromosome band 10q24, and loss of 1p11‐p21 and 10q26‐qter (all simultaneously present in 6/7 MIFS); a breakpoint in or nearTGFBR3in chromosome 1 was found in four of these tumors. Amplification and overexpression ofVGLL3was a consistent feature in MIFS and MIFS‐like tumors with amplicons in 3p11‐12. The significant molecular genetic outcome of the recurrent t(1;10) could be loss of genetic material from 1p and 10q. Other recurrent genomic imbalances in MIFS, such as homozygous loss ofCDKN2Aand 3p‐ and 13q‐deletions, are shared with other sarcomas, suggesting overlapping pathogenetic pathways.