Oil-induced murine plasmacytomas typically carry c-myc-activating non-random reciprocal chromosomal translocations that take the form of either a T(12;15) that fuses the c-myc proto-oncogene to an immunoglobulin heavy chain switch region or a T(6;15) that juxtaposes the Pvt-1 locus, located 220 kb 3' of c-myc, to the immunoglobulin light china locus, C kappa. In this report we show that the plasmacytoma ABPC 60 harbors a novel c-myc-activating T(12;15) in which the chromosome 15 breakpoint occurs in the Pvt-1 region, resulting in the head-to-tail juxtaposition of the Pvt-1 major breakpoint cluster to the IgA switch region. Restriction mapping and nucleotide sequencing of this atypical translocation indicate that a paracentric inversion in chromosome 12 must have preceeded the translocation. This is the first example of a T(12;15) with a break 3' of the c-myc gene. The rearrangement places the 3' C alpha enhancer (3' alpha E) greater than 200 kb downstream of the c-myc promoters, however c-myc mRNA levels are similar to those observed in plasmacytomas with typical T(12;15)s that translocate 3' alpha E much closer (15-25 kb) and upstream of c-myc. The up regulation of c-myc that results from this rearrangement is thought to be brought about by the interaction of the c-myc promoters with the IgA enhancer element that has been strategically relocated into the Pvt-1 region.