Deregulated expression of the c-myc gene appears to play an important role in the development of Burkitt’s lymphoma (BL) and certain other lymphoid tumors. Physiologic regulation of the c-myc gene is complicated, involving the interplay of distinct transcriptional and post transcriptional mechanisms. There are many regulatory elements that bind to the upstream region of the c-myc gene, however, this chapter will focus on the factors that bind to the intron I region of this gene and will discussed the possible role intron I sequence may have in the regulation of the c-myc gene.