We examined 800 NSCLC specimens (400 lung adenocarcinomas, 400 squamous cell carcinomas) using immunohistochemistry, RT-qPCR, Western blotting, and spatial transcriptomics to profile SOX18, SOX30, and related signaling partners (SOX7, SOX17, MEF2C—Myocyte Enhancer Factor 2C, VCAM1—Vascular Cell Adhesion Molecule 1, p-STAT3—Signal Transducer and Activator of Transcription 3). Here, STAT3 is linked to squamous cell carcinoma.