The present invention provides transgenic fish whose genome has stably-integrated therein an oncogene operably linked to a promoter. Methods of making the transgenic fish and methods for their use are also provided. In one embodiment, the transgenic fish may advantageously be utilized in methods of screening for drugs or agents that modulate oncogene-mediated neoplastic or hyperplasic transformation, or that modulate sensitivity to chemotherapy or radiation therapy. In another embodiment, the transgenic fish may be used methods of identifying mutations that modulate oncogene-mediated neoplastic or hyperplastic transformation, or that modulate sensitivity to chemotherapy or radiation therapy.