Comparison of the Anaplastic Lymphoma Kinase (ALK) mutations found in neuroblastoma with the secondary crizotinib-resistant mutations reported in non-small-cell-lung-cancer (NSCLC) and inflammatory myofibroblastic tumours (IMT) highlights some interesting features. Resistant mutations (red) generally cluster the inhibitor and ATP binding site (ADP, cyan) and strongly activating neuroblastoma-associated ALK mutations (blue) occur nearby or around the putative residues that are important for initial activation of ALK (αC-helix; green, A-loop; teal) activity. Two exceptions are the F1174 and G1269 mutations (purple), which are mutations found in both neuroblastoma and resistant NSCLC patients. Regulatory spine (light pink) and Catalytic spine (lime green) are shown.