cDNA libraries enriched with sequences that are differentially transcribed in normal and tumor tissues were prepared using the subtractive hybridization of mixtures of cDNAs from ten patients with squamous cell lung cancer and the corresponding mixtures of cDNAs from normal tissues of the same patients. An analysis of the libraries revealed two genes, NOLA2 and RPS3A, whose expression in patients with squamous cell lung cancer increased by 70%. A high frequency of enhanced expression of these genes in the cancer makes them highly informative markers of squamous cell lung cancer, which, together with other markers, can be used for reliable diagnosis of the disease.