Clinically, human glioblastoma (GBM) may develop de novo or from a low-grade glioma (secondary GBM), and molecular alterations in the two pathways may differ. This study examined the status of Survivin expression and apoptosis in 30 primary and 26 secondary GBMs. Our results show that cytoplasmic Survivin positivity was significantly (Po0.001) more frequent in primary GBMs (83%) than that in secondary GBMs (46%). In addition, an inverse correlation of cytoplasmc Survivin positivity with GBM apoptotic index, and a positive association between cytoplasmic Survivin and size of the tumours were observed. These results suggest that cytoplasmic Survivin, via its antiapoptotic function, may be involved in the tumorigenesis of many primary GBMs, but only in a small fraction of secondary GBMs. Furthermore, the overall progression times from low-grade precursor lesions to secondary GBMs were significantly shorter (Po0.05) in cytoplasmic Survivin-positive cases (mean, 15.6 months) than those in Survivin-negative cases (mean, 23.8 moths), and the positive expression level of Survivin in cytoplasm was upregulated in most secondary GBMs when compared to matched pre-existing low-graded lesions. These results suggest that the increased accumulation of Survivin in the cytoplasm of more malignant glioma cells may prove to be a selective advantage, thus accelerating progression to a more aggressive phenotype. British Journal of Cancer (2006) 94, 108–114. doi:10.1038/sj.bjc.6602904 www.bjcancer.com Published online 13 December 2005