Identification of novel targets and biomarkers, such as microRNAs, is extremely helpful to understand the pathogenetic mechanisms in a disease like multiple sclerosis (MS). We tested the expression profile of 1145 microRNAs in peripheral blood mononuclear cells (PBMCs) of 19 MS patients and 14 controls, and we further explored their function by performing a whole-genome mRNA profiling in same subjects and using bioinformatic prediction tool. A total of 104 miRNAs have been identified as deregulated in MS patients; 2/10 which ranked highest (let-7g and miR-150) have been validated in a replication sample, leading to the identification of putative target genes.