To identify novel human head-and-neck squamous cell carcinoma (HNSCC)-associated Ly-6 members with squamous cell-associated expression patterns, a comprehensive gene-screening was performed, followed by expression analysis. Using this approach, the Ly-6K gene was identified as a novel member of the human Ly-6 family. Results show that Ly-6K is a potential target antigen for the diagnosis and therapy of HNSCC.