A new affinity-based spin column procedure has been developed for highly specific isolation of exosomes and other extracellular vesicles (EVs) from serum or plasma, as well as for vesicular RNA content (exoEasy and exoRNeasy protocols). Results indicate that vesicular RNA (incl. miRNA) can be separated from non-vesicular RNA, and that fully intact long RNAs as well as miRNAs can be recovered and successfully profiled. In addition, the influence of different sample collection, handling and processing devices and workflows on RNA representation has been tested. Learning objectives: 1. Isolation of EVs and vesicular RNA from serum, plasma, and other biofluids 2. Detection and profiling of extracellular miRNAs and long RNAs 3. Challenges and solutions associated with sample collection and processing of biofluids for analysis of EVs and vesicular content