Prostate cancer (PCa) is the second most frequently cause of cancer death among men in the US and Uruguay. Our work aims to understand the role of cancer stem cells (CSC) in PCa initiation and progression. We have developed an in vitro model for prostate CSC (PCSC) differentiation form prostatospheres (PS) (Duhagon et al, 2010) which allowed us to study the differential expression of microRNAs (miRs) during this process. MiRs are known to be extensively deregulated in cancers and can be used for disease stratification, follow up, prognosis and therapeutics. Our research seeks the involvement of miRs in PCSCs differentiation through the discovery of their cellular effect and their molecular mechanism of action. Using miRs arrays we have identified miRs modulated during PCSC differentiation and we selected three of them for detailed study: miR-301b, miR-183, and miR-886-3p. We have just initiated the study of miR-183 and miR-886-3p, which has lead us to propose an oncogenic and tumor suppressor role in PCa respectively.