The salient findings of our study are: (i) significant increase in S100A7 expression (cytoplasmic/nuclear) in squamous cell hyperplasia, dysplasia and HNSCC in comparison with normal oral tissues; (ii) cytoplasmic S100A7 expression distinguishes squamous cell hyperplasia, dysplasia and HNSCC from normal mucosa with high specificity and PPV; (iii) significant increase in nuclear S100A7 accumulation in HNSCC as compared to dysplasia; and (iv) potential of nuclear S100A7 as a marker of poor prognosis of HNSCC. This evidence concerns the gene S100A7 and dysplasia.