To search for genes that can collaborate with myc in lymphomagenesis, we exploited retroviral insertional mutagenesis in E mu-myc transgenic mice. Moloney murine leukemia virus accelerated development of B lymphoid tumors. Three quarters contained a provirus within the known pim-1 or pim-2 loci, new loci bmi-1 and emi-1, or combinations of these. bmi-1 insertions predominated, occurring in half the tumors, and resulted in elevated bmi-1 mRNA levels. Significantly, the bmi-1 gene, which is expressed in diverse normal cells, encodes a Cys/His metal-binding motif (C3HC4) that resembles those in several DNA-binding proteins and defines a new category of zinc finger gene. Thus, myc-induced lymphomagenesis can entail the concerted action of several genes, including the presumptive nuclear regulator bmi-1.