Themyconcogene was originally identified as a transduced allele (v-myc) in the genome of a highly oncogenic avian retrovirus. The protein product (Myc) of the cellular c-mycproto-oncogene represents the key component of a transcription factor network controlling the expression of a large fraction of all human genes. Myc regulates fundamental cellular processes like growth, metabolism, proliferation, differentiation, and apoptosis. Mutational deregulation of c-mycleading to increased levels of the Myc protein is a frequent event in the etiology of human cancers. In this chapter, we describe cell systems and experimental strategies to monitor and quantify the oncogenic potential ofmycalleles and to isolate and characterize transcriptional targets of Myc that are relevant for the cell transformation process. We also describe experimental procedures to study the evolutionary origin ofmycand to analyze structure and function of the ancestralmycproto-oncogenes.