Our study investigated, in an NPM-ALK-positive cellular model, the differences in activity within a panel of clinically relevant second-generation ALK inhibitors (AP26113, ASP3026, alectinib, and ceritinib) against six mutated forms of ALK (NA C1156Y, NA L1196M, NA L1152R, NA G1202R, NA G1269A, NA S1206Y) associated with crizotinib resistance in ALK-positive NSCLC patients. This evidence concerns the gene ALK and non-small cell lung carcinoma.