The data in this report clearly indicate that the form (structure) in which selenium is used is the most critical determinant of success in future clinical trials. Synthetic organoselenium compounds can be tailored to achieve greater chemopreventive efficacy with minimal toxic side effects by structural modifications. We demonstrated that 1,4-phenylenebis(methylene)selenocyanate is a powerful chemopreventive agent against the development of experimental colon, mammary, lung, and oral carcinogenesis. On the basis of metabolism studies of organoselenium compounds and those reported in the literature, our working hypothesis is that aromatic selenol intermediates are important entities in cancer chemoprevention. In addition, we suggest that 1,4-phenylenebis(methylene)selenocyanate not only serves as a chemopreventive agent, but it may be valuable in preventing metastatic diseases in future studies in the clinic.