The purpose of this review is to discuss chondroitin sulfate (CS) proteoglycan 4 (CSPG4) as a tumour biomarker and explain why its expression might be considered in clinical decision making for patients with SCCs, including those of the head and neck, and those arising from rare genetic disorders, such as epidermolysis bullosa (EB). This evidence concerns the gene CSPG4 and neoplasm.