Medulloblastoma is the most common malignant brain tumor in children, often resulting from aberrant activation of the hedgehog signaling pathway. A 26-year-old man with metastatic medulloblastoma, refractory to multiple therapies, was treated with GDC-0449, a novel hedgehog pathway inhibitor. Treatment led to rapid regression of the tumor and reduction of symptoms. Molecular analyses of the tumor suggested activation of the hedgehog pathway, including loss of heterozygosity and somatic mutations in the PTCH1 gene, a key negative regulator of hedgehog signaling. The patient's response to GDC-0449 highlights the potential of hedgehog pathway inhibitors in treating medulloblastoma, despite the tumor's advanced stage and extensive metastasis. However, the patient's disease progressed rapidly after the initial response, and he died in September 2008. This case report underscores the importance of further research into the mechanisms of resistance to hedgehog pathway inhibitors and the need for careful monitoring in clinical trials.Medulloblastoma is the most common malignant brain tumor in children, often resulting from aberrant activation of the hedgehog signaling pathway. A 26-year-old man with metastatic medulloblastoma, refractory to multiple therapies, was treated with GDC-0449, a novel hedgehog pathway inhibitor. Treatment led to rapid regression of the tumor and reduction of symptoms. Molecular analyses of the tumor suggested activation of the hedgehog pathway, including loss of heterozygosity and somatic mutations in the PTCH1 gene, a key negative regulator of hedgehog signaling. The patient's response to GDC-0449 highlights the potential of hedgehog pathway inhibitors in treating medulloblastoma, despite the tumor's advanced stage and extensive metastasis. However, the patient's disease progressed rapidly after the initial response, and he died in September 2008. This case report underscores the importance of further research into the mechanisms of resistance to hedgehog pathway inhibitors and the need for careful monitoring in clinical trials.