Although the most frequent translocation partner of EWS is FLI1, with the common fusion joining EWS exon 7 in frame with FLI1 exon 6 (type 1 fusion), there are several other EWS-FLI1 type fusions, as well 5–10% of patients with ESFT have an EWS partner ERG. Our method focused on ESFT exo-proteins to immuno-enrich tumor-associated circulating EVs for the subsequent detection of EWS-FLI1 Types I, II, and III and EWS-ERG fusion transcripts within pediatric patient plasma. Here, EWSR1 is linked to neoplasm.