Flowchart for classification of multiple NCSLC using histology*and NGS. *Histologic features may not be sufficiently distinctive for squamous cell carcinoma. Molecular testing should be performed for all cases. 1, this scenario supports SPLCs only if adequate tumor content has been confirmed histologically in the driver-negative tumor (see Supplementary Materials and Method 2 for details). 2, applicable to NGS only but not major driver-only testing. 3, if only a single alteration is shared, the degree to which this supports IPMs should be determined on the basis of prevalence of that alterations in a given population as well as overall clinicoradiologic context (see Supplementary Materials and Method 2 for details). 4, driver negative in both tumors would benefit from broad panel NGS for comprehensive comparison of mutation profiles (see Supplementary Materials and Method 2 for details). AIS, adenocarcinoma in situ; MIA, minimally invasive adenocarcinoma.