Objective: The molecular hallmark of Burkitt Lymphoma (BL) is a dysregulation of MYC oncogene, due to one of the three translocations leading to IG-MYC fusion. However, about 10 % of BL cases lack an identifiable MYC rearrangement, although no significant difference of MYC expression among cases has been observed. Additional mechanisms alternative to translocations were explored by microRNA profiling. Method: Ten MYC translocation-positive and ten MYC translocation-negative formalin-fixed and paraffin-embedded BL specimens were used for this study. For microRNA and gene expression profile, the samples were hybridized on the miRCURY™ LNA Array and the Illumina DASL whole genome Assay, respectively. Results: Our results identified a panel of four microRNAs which are differentially expressed between the two groups. Importantly, these microRNAs control relevant biological processes, such as the angiogenesis, apoptosis and cell proliferation, according to Gene Ontology categories. Furthermore, the impact of microRNA dysregulation on the gene expression pattern identified genes which more likely are regulated by the selected microRNA. Conclusion: Using this approach, we showed a clear-cut microRNA and gene signature between MYC translocationpositive and negative BLs. The identification of specific altered microRNAs may represent an alternative molecular mechanism leading to MYC over-expression in the absence of genetic alteration in cancer.