Squamous cell carcinomas should be tested for EGFR (if positive, first-line therapy should consist of Erlotinib, Afatinib or Gefitinib), ALK (if positive, consider Crizotinib or Ceritinib), ROS1 (if positive, consider Crizotinib) and PD-L1 (if PD-L1 positive with the aforementioned markers either negative or of unknown status, consider systemic immune checkpoint inhibitors, Nivolumab, Pembrolizumab, Atezolizumab or systemic therapy with Docetaxel, Pemetrexed, Gemcitabine or Ramucirumab + Docetaxel). This evidence concerns the gene CD274 and squamous cell carcinoma.