The apparent lack of a specific biologic basis for the higher metastatic burden of de novo vs. secondary metastatic EGFR+ NSCLC contrasts a similar constellation in the closely related ALK+ NSCLC: here, an increased number of metastatic sites at initial diagnosis is also associated with a worse baseline ECOG PS (28), but linked to the special biologic properties of EML4-ALK variant 3 (V3) that enhance cancer dissemination (28–31). This evidence concerns the gene EGFR and non-small cell lung carcinoma.