Malignant gliomas are characterized by their invasiveness and angiogenesis. Matrix metalloproteinases (MMPs) degrade extracellular matrix and create a more permissive environment for cell invasion. We aimed to investigate for the presence of inter- and intratumoral heterogeneity in MMP-2 messenger RNA (mRNA) expression by means of quantitative analysis and to evaluate its prognostic impact in glioma patients. Representative sections from the center and periphery of tumors resected en bloc were taken fresh for study, stained with hematoxylin/eosin for histological evaluation, and immunohistochemically analyzed for Ki-67. MMP-2 mRNA expression was evaluated by real-time reverse transcriptase polymerase chain reaction (RT-PCR). There was MMP-2 expression in all analyzed tumors. By topographical dissection of surgical specimens, we found no differences in cell proliferation or density but significant differences with regard to MMP-2 mRNA expression between central and peripheral regions, being highest at the center of malignant gliomas. MMP-2 mRNA expression showed no prognostic influence on overall or disease-free survival. Our results demonstrate that MMP-2 is differentially expressed in central and peripheral regions of gliomas. Further studies are necessary to clarify the significance of these findings and their possible relevance in clinical practice.