We have compared proviral integrations near (putative) proto-oncogenes in Moloney murine leukemia virus-induced primary and transplanted T cell lymphomas. We previously found proviruses integrated near c-myc, pim-1, and N-myc in primary tumors (Selten et al., 1984; Van Lohuizen et al., 1989a; Van Lohuizen et al., 1989b). We have now identified an additional common proviral integration site, called pim-2, that carries somatically acquired proviruses in the majority of transplanted tumors. In primary tumors integration near pim-2 is usually undetectable or present in only a minor fraction of the tumor cells. This subpopulation selectively grows out upon transplantation. Insertion near pim-2 is a relatively late event in tumorigenesis and is often preceded by proviral insertions in other common insertion sites, yielding tumor clones which carry proviruses in up to three different common insertion sites within the same cell (c-myc, pim-1 and pim-2). The data suggest that pim-2 plays an important role in tumor progression.