Matrix metalloproteinases play an important role in the invasion of tumor cells and the progression of cancer. The 72 kDa type IV collagenase, a matrix metalloproteinase 2 (MMP-2) has been shown to contribute to the invasion and metastasis in diverse malignant neoplasms. OBJECT: To elaborate the potential role of MMP-2 in brain tumor invasion we studied the expression and localization of this enzyme protein in 101 brain tumors representing different types of brain neoplasms. For the first time, we also correlated the expression of MMP-2 protein to patient survival. METHODS: Using immunohistochemistry and a monoclonal antibody specific for MMP-2 we found that MMP-2 protein was primarily localized in tumor cells and vasculature cells as well as inflammatory cells. The expression of MMP-2 was absent or negligible in benign tumors (pilocytic astrocytoma and meningioma). Thirty-three percent (6/18) of astrocytomas, 38% (3/8) of anaplastic astrocytomas, 14% (1/7) of anaplastic oligodendrogliomas, 54% (19/35) of glioblastomas and 100% (6/6) of metastatic brain tumors were positive for MMP-2. A correlation between MMP-2 expression and survival was found in malignant brain tumors. The mean survival of patients with an MMP-2 negative tumor was 36 months, when it was only 7-14 months in patients with an MMP-2 positive tumor. CONCLUSIONS: Our data suggest that MMP-2 is associated with histological malignancy and poor survival in brain tumors.