Several databases were searched using the keywords “perineural invasion,” “immunotherapy,” and “cutaneous squamous cell carcinoma.” Cemiplimab, an anti–PD-1 agent, received US Food and Drug Administration approval based on the phase 2 EMPOWER cutaneous SCC (cSCC)-1 trial and a phase 1 trial (NCT02383212) for patients with locally advanced or metastatic cSCC ineligible for curative surgery or RT [17]. This evidence concerns the gene PDCD1 and skin squamous cell carcinoma.