BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules (21-24 nt) that negatively regulate gene expression, either by repression of translation or by degradation of messenger RNA. These molecules are involved in many important processes including cell differentiation, neurogenesis, formation of nervous system and others. Mesial temporal lobe epilepsy and epilepsy caused by cortical dysgenesis are among the leading causes of drug resistant epilepsy. OBJECTIVES: The objectives of this study were to characterize the expression profile of miRNAs and to investigate their regulation in mesial temporal lobe epilepsy (MTL) and in focal cortical dysplasias (FCDs). METHODS: Total RNA was extracted from hippocampal and neocortical tissue, maintained in paraffin or fresh-frozen, from patients who underwent surgery for seizure control. For comparison we used tissue obtained from autopsy. RNA was extracted and used in real time PCR reactions (157 miRNAs analyzed) or microarray chips (847 miRNAs analyzed). RESULTS: Bioinformatics analyzes identified three miRNAs with expression significantly different in patients with MTLE: let-7d, miR-29b and miR-30d; while in patients with FCDs we found 23 microRNAs differentially expressed. In addition, we found that different pathological forms of had different molecular signatures. CONCLUSIONS: The possible genes regulated by miRNAs with differential expression in tissue with mesial temporal sclerosis (MTS) are mainly related to neurogenesis and apoptosis. While in DCFs they were predominantly related to cell proliferation and migration. Our results demonstrate the importance of miRNA regulation the in molecular processes that lead to the lesions present in the MTS and the FCDs.