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WOX1 is frequently upregulated, along with increased Tyr33 phosphorylation (p-WOX1), during progression of breast, prostate and probably other types of cancers to a pre-metastatic stage. In contrast, invasive or metastatic cells loss WOX1 expression. Here, we examined the expression of WOX1 in different types of brain tumors in Caucasians and Asians. Immunohistochemistry revealed that protein and gene expressions of WOX1 are low in normal cortical neurons but present along axon fibers. Compared to normal tissues, increased WOX1 protein expression along with p-WOX1 is shown in transitional and atypical meningiomas, astrocytomas, ependymomas, and schwannomas. WOX1 is further increased by more than 2-3 folds in microcystic and malignant meningiomas, high grades astrocytomas and glioblastomas (GBMs). Nuclear translocation is present in GBM. Similar expression profiles were also observed for WWOX mRNA in meningiomas and astrocytomas, as determined by in situ hybridization. Tissue microarray analysis further confirmed that the protein levels of WOX1 and WOX3, but not WOX2, were significantly upregulated in benign solid brain tumors. In conclusion, upregulation of WOX1 and family proteins, along with p-WOX1, is probably associated with progression of brain tumors from benign to malignant. [ABSTRACT FROM AUTHOR]