The anaplastic lymphoma kinase (ALK) was recently found to be mutated in neuroblastoma. Scott Bresler and colleagues used ALK-expressing neuroblastoma cell lines and xenografts to assess the efficacy of the ALK and MET tyrosine kinase inhibitor crizotinib. They found that neuroblastoma cell lines that had either amplified wild-type ALK or the ALK mutant R1275Q were sensitive to crizotinib. However, neuroblastoma cell lines with F1174L ALK mutations were relatively resistant to this drug, owing to the increased ATP-binding affinity of this mutant. The authors propose that patients with neuroblastomas that have the F1174L mutation might still respond to either high doses of crizotinib or to ALK inhibitors that have an increased binding affinity compared with crizotinib.