Previous epidemiology studies have shown association between coal burning and human lung cancer. To confirm relationship of coal burning to lung cancer formation and progression the expression of p53 and c-myc in 13 mouse lung cancer induced by coal-burning smoke and 5 mouse lung tissue control was studied by DNA-RNA in situ hybridization (ISH). Nine of 13 specimens showed c-myc overexpression but it occurred only 1 in 9 in the adjacent tissue. There was overexpression of p53 mRNA in all 13 lung cancer and 5 adjacent tissues. None in the controls was expression of p53 and c-myc detected. When compared to controls, there was significant higher expression of c-myc gene (P = 0.002) and p53 gene (P = 0.0001). The results confirm that overexpression of p53 and c-myc are common molecular events of lung cancer by coal-burning smoke and provide further evidence that smoke from coal burning is a causative agent of lung cancer.