LSCC is a common type of lung cancer and accounts for approximately 30% of all lung cancers. We have used a combination of subtraction and cDNA microarray technology to identify genes preferentially over-expressed in LSCC. Here we report extensive molecular characterization of two novel full-length cDNA sequences, L530S and L531S. Although L530S and L531S were found to be differentially over-expressed in LSCC, the expression profiles for these two genes were not identical. L530S expression was specifically elevated in LSCC whereas L531S transcript was up regulated in both LSCC and head and neck squamous cell carcinoma samples. L530S is a homologue of p53, and L531S belongs to a new member of serine proteinase inhibitors with significant homology to SCCA1 and SCCA2. Furthermore, L531S protein was found to be expressed in lung cancers by IHC analysis. The distinct as well as similar expression profiles exhibited by L530S and L531S suggest that each gene may play a unique role for tumorgenesis of LSCC. Identification of these genes not only allows us to further explore their diagnostic and therapeutic potentials for LSCC, but also provides us with additional tools and reagents for understanding the biology behind LSCC, and differentiating LSCC from other types of lung cancer at the molecular level.