Expression of CD44 has been implicated in tumor growth and metastasis. Here we demonstrate CD44 expression in primary human brain tumors (n = 44) and brain metastases (n = 7) by RT-PCR and immunohistochemistry. Standard CD44 was found to be expressed by the majority of primary brain tumors and brain metastases. For the first time to our knowledge, CD44 expression is demonstrated for acoustic neurinomas and pituitary adenomas. Exon-specific analysis by RT-PCR and indirect immunofluorescence revealed expression of alternatively spliced CD44 isoforms in the group of brain metastases only. However, in one glioblastoma multiforme, expression of CD44v5 and CD44v6 was found immunohistochemically. This tumor took an unusual clinical course giving rise to multiple intrahepatic and lymph node metastases. Quantitatively different expression of standard CD44 in gliomas versus meningiomas is reported (p < 0.01).