Flow cytometry analysis of B-cell surface expression markers, performed on HNSCC tumor tissue, isolated PBMCs and healthy oral mucosa samples, revealed significantly higher levels of CD86+ activated and CD86+/CD21- antigen-presenting B-cell phenotypes in tumor samples compared with PBMCs and non-cancerous mucosa, while memory B-cells characterized by IgD−/CD27+ phenotype were increased in HNSCC patients’ tumor tissue and peripheral blood as opposed to healthy donors. Here, CD86 is linked to head and neck squamous cell carcinoma.