Recent studies combining state-of-the-art molecular profiling with detailed clinical annotation have identified two molecular risk factors associated with TKI failure in ALK-driven NSCLC: echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variant V3 [3,4,5] and the presence of tumor protein p53 gene (TP53) mutations at initial diagnosis [6,7,8]. The gene discussed is ALK; the disease is non-small cell lung carcinoma.