In this study we utilized the SCC‐13 cell line, publicly available cSCC and head and neck SCC (HNSCC) patient expression data, patient‐derived skin and cSCC tissues and a mouse model of cutaneous carcinogenesis to evaluate PANX1 and PANX3 expression in cSCC compared to normal skin and their role in cSCC malignancy. This evidence concerns the gene PANX3 and head and neck squamous cell carcinoma.