Specificity of the immunocapture for MTEX was verified by demonstrating that MTEX isolated from various melanoma cell lines showed the presence of CSPPG4 on all sEVs albeit at various expression levels; only MTEX isolated from plasma were CSPG4+, while non-MTEX were CSPG4 (-); sEV obtained from plasma of HDs were CSPG4 (-) and only MTEX were highly enriched in melanoma-associated antigens (MAA), TYRP2, Melan A, Gp100, VLA4; only non-MTEX were CD3+, while MTEX were CD3 (−). Here, MLANA is linked to melanoma.