We have identified a potential serum marker for glioblastoma multiforme (GBM) using microarray analysis from samples of GBM. We compared the gene expression profile of 19 gliomas to pooled normal brain by competitive hybridization of RNA from each tumor sample to a pooled sample of RNA isolated from normal brain tissue using the Incyte 10,000 gene expression array. The most differentially expressed gene in this analysis encodes a secreted glycoprotein and is referred to as YKL-40. YKL-40 mRNA was detected in the GBM samples with a range of 3- to 62-fold elevation over normal brain. It has been reported previously that this protein is expressed in pathologic conditions of extracellular matrix degradation and angiogenesis, such as rheumatoid arthritis, severe osteoarthritis, hepatic fibrosis, primary colorectal cancer, and metastatic breast cancer. These data suggest YKL-40 may be involved in extracellular matrix degradation and/or angiogenesis. Western blot analysis of glioma samples for YKL-40 protein levels revealed substantial elevation in approximately 65% of GBMs and undetectable levels in lower-grade gliomas (grade II and III) or normal brain tissue. We performed ELISA analysis on serum samples of glioma patients to determine whether this protein would correlate with the presence of tumor and tumor grade or burden. YKL-40 serum levels were substantially elevated in many of the GBM patients. Statistical analysis of these data indicates that in patients with glioma, serum YKL-40 levels correlate with tumor grade and potentially tumor burden in GBM.