Krystel-Whittemore M, Taylor MS, Rivera M, et al. - Sixty-three consecutive cases examined for EWSR1 gene fusions between 2015 and 2018 were involved in this study in order to investigate the EWSR1 fusions recognized over a 3-year period, using different methods, their relationship with particular entities and potential discovery of novel partners and correlations. Of the 28 cases with dual testing, 24 were positive via both assays for an EWSR1 gene fusion, three were discordant with a positive fluorescence in-situ hybridization (FISH) assay and a negative NGS assay, and one was discordant with a negative FISH assay although it was a positive NGS assay. Three novel fusions were recognized, ie, a complex rearrangement involving three genes (EWSR1/RBFOX2/ERG) in Ewing sarcoma, a EWSR1/TCF7L2 fusion in a colon adenocarcinoma, and a EWSR1/TFEB fusion in a translocation-associated renal cell carcinoma. Both colonic adenocarcinoma and renal cell carcinoma had not been formerly related to EWSR1 rearrangements. Discovery of a particular partner had an effect on the histological diagnosis and patient management in a subset of cases. Hence, for the discovery of known and novel EWSR1 rearrangements and fusion partners, the use of a targeted NGS-based fusion assay was concluded as better than EWSR1 break-apart FISH, especially provided the emerging understanding that different fusion partners lead to various diseases with different prognostic and therapeutic inference.