Betulinic acid, a pentacyclic triterpene of the lupane type, is a cytotoxic agent for malignant melanoma. It was identified as a selective inhibitor of melanoma inducing apoptosis by a direct effect on mitochondria independent of accumulation of wild-type p53 protein and independent of death-inducing ligand/receptor systems such as CD95. Mitochondrial perturbations on treatment with betulinic acid resulted in the release of soluble apoptogenic factors such as cytochrome c or alternative reading frame from mitochondria into cytosol, where they induced activation of caspases. Betulinic acid may be a promising new agent in the treatment of neuroectodermal tumors including neuroblastoma.