Pleomorphic xanthoastrocytoma (PXA) is a rare, superficially located astrocytic glioma of children and young adults, which is associated with a relatively favorable prognosis. Here we report on the expression of the hematopoietic progenitor cell and vascular endothelial cell associated antigen CD34 in PXAs. We found CD34 immunoreactivity in various fractions of tumor cells in 44 of 60 PXAs investigated (73%). CD34 expression was more common in PXAs of WHO grade II (37 of 44 tumors, 84%) than in PXAs with anaplastic features (7 of 16 tumors, 44%). Immunoreactivity for CD34 was also commonly detected in single or clustered dysplastic neural cells within the cerebral cortex adjacent to the PXAs. Reverse transcription-PCR revealed that PXAs express the full-length CD34 transcript and a known splice variant encoding a truncated form of CD34. Both transcripts were detectable at higher levels in PXAs as compared to diffuse astrocytomas and non-neoplastic brain tissue. Taken together, our findings demonstrate that PXAs frequently express CD34 not only in vascular endothelial cells but also in tumor cells and in dysplastic cells of the adjacent cortex. Therefore, immunostaining for CD34 may be a helpful tool for the histological differential diagnosis of PXAs.