In pairwise analyses of 89 matched normal and tumor samples from lung cancer patients, we found EphB4 to be significantly overexpressed compared to paired normal tissues in adenocarcinoma (n = 41; 4.3-fold mean difference), large cell carcinoma (n = 15; 2.9-fold mean difference), small cell carcinoma (n = 13; 2.4-fold mean difference), and squamous cell carcinoma (n = 10; 2.7-fold mean difference) subtypes. This evidence concerns the gene EPHB4 and squamous cell carcinoma.