Classic biphasic pulmonary blastoma (CBPB) is a rare and aggressive type of non–small cell lung carcinoma (NSCLC) presenting in adults in the fourth to fifth decade. The prognosis is poor and after surgical resection, therapeutic options are often limited. ROS1 is a proto-oncogene receptor tyrosine kinase that has been identified in some types of NSCLC. We report a case of a 36-year-old woman with CBPB, which was subsequently found to have a ROS1 rearrangement. This is the first reported case of a ROS1-rearranged CBPB. This finding has therapeutic implications as these tumors have the potential to be treated with receptor tyrosine kinase inhibitors.