Well-differentiated fetal adenocarcinomas and biphasic blastomas are types of lung cancer that contain glands that mimic the appearance of fetal lung. Biphasic blastomas also show a primitive embryonic stroma. Despite histological similarities leading these two tumors to be classified as pulmonary blastomas, they have distinct clinical and prognostic features. Little information is available on genetic changes in these tumors because they are rare; therefore, the authors studied nine biphasic blastomas and 12 well-differentiated fetal adenocarcinomas for the presence of mutations in the p53 gene. Mutations in the p53 gene are common in other lung cancers, and the type of mutation in the p53 gene can provide information about the original or inciting mutagens. The authors found five biphasic blastomas (42%) had mutations in the p53 gene by immunohistochemical and molecular analysis, whereas none of the well-differentiated fetal adenocarcinomas contained mutations. These results provide molecular support for the significance of distinguishing between well-differentiated fetal adenocarcinoma and biphasic blastoma histologically and identify several types of p53 gene mutations that occur in these tumors.