Retroviral insertional mutagenesis has been applied to identify oncogenes that are important for both human and rodent carcinogenesis. The method reveals not only primary oncogenes but also cooperative genes that might be affected as second or third hits in multistep carcinogenesis. The use of genetically engineered mice such as NUP98-HOXA9 transgenic mice enabled efficient identification of cooperative genes, which provides important information for the molecular pathway in carcinogenesis/leukemogenesis. With use of the retrovirus mediated gene transfer system, retroviral insertional mutagenesis will provide invaluable information to understand genetic interaction in complex mechanisms of carcinogenesis.