Altogether, elevated expression of S100A8 and S100A9, upregulation of LYPLA1 and concomitant depletion of specific lysophospholipids, paralleled with an accumulation of specific phospholipids were identified as potential tumor markers via imaging mass spectrometry and immunohistochemistry-based screening of HNSCC specimens. This evidence concerns the gene S100A9 and head and neck squamous cell carcinoma.