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. The gene discussed is LYPLA1; the disease is head and neck squamous cell carcinoma.