The c-fgr gene is a member of the tyrosine kinase family of proto-oncogenes and is expressed exclusively in hemopoietic cells. We found that c-fgr was expressed at high levels in a limited subset of murine monocyte/macrophage tumors that were induced by the c-myc oncogene, in cells representing late stages of monocyte differentiation. A cDNA clone was isolated from a library made from a monocyte tumor cell lines using a human c-fgr and v-fgr probe. The composite nucleotide and predicted amino acid sequence of the cDNA indicates that it represents the complete coding sequence for the murine c-fgr gene. Comparison of the N-terminal human and mouse c-fgr amino acid sequences indicates regions of identity that are not homologous to other tyrosine kinases. Interestingly, these regions share a limited but significant homology to two viral proteins, adenovirus E1b and HIV nef. In addition, there are other regions of homology that are shared by several tyrosine kinases and other non-kinase proteins which may be important for subcellular localization.