We observed that cSCLC harbored significant genomic alterations and oncogenic mutations, which varied across LCC, LCNEC, SCLC, and ADC/SCC, featuring TP53 and RB1 mutations in SCLC and LCC/LCNEC, MYC CNV gain in SCLC, and EGFR mutations in ADC/SCC or paired SCLC. Here, RB1 is linked to leukoencephalopathy with calcifications and cysts.