Mechanisms of retrovirus induced transformation have been intensively and successfully investigated in recent years. The most important consequence of the developed techniques and the information obtained is the demonstration of the presence in the normal invertebrate and vertebrate, including human, cells of genes capable of inducing neoplastic transformation. These cellular genes have been identified by hybridization of normal cellular DNA with retroviral transforming sequences and by the demonstration of the biological activity of cellular DNA from different tumors in mouse cell transfection assays. These genomic sequences have been called proto-oncogenes to distinguish them from their retroviral equivalents, to recall their cellular origin and to differentiate them from their activated oncogenic counterparts. The different mechanisms involved in the activation of proto-oncogenes include point mutation, deletion, promoter insertion, translocation and amplification. Recent evidence suggest that transformation is a multistep process in which different oncogenes may play different roles.