In the present work, we performed extensive research on the proteomic make-up of plasmatic S-EVs of ALCL patients compared to healthy donors, and we propose S-EV tenascin C (TNC), osteopontin (SPP1/OPN) and heat shock protein 90-kDa isoform alpha 1 (HSP90AA1) as potential biomarkers for ALCL prognostic stratification. Here, SPP1 is linked to anaplastic large cell lymphoma.