Two cases of non-Hodgkin's lymphoma (NHL) of B-cell origin with reciprocal chromosome translocations involving the 3q27 band and loci for the immunoglobulin genes are described. In case 1, [t(3;14)(q27;q32)], the 14q32 band for the immunoglobulin heavy chain gene was involved, and in case 2, [t(3;22)(q27;q11)], the reciprocal breakpoint was the 22q11 band where the immunoglobulin lambda light chain gene is located. Although the two patients shared some clinical features, the lymphomas varied in histologic phenotypes; in case 1, the lymphoma being a diffuse large cell subtype, whereas in case 2, the lymphoma being the high grade small noncleaved cell lymphoma. Thus, the consistent association of the 3q27 translocation with a specific subtype of NHL remains to be determined. Southern blot analysis of the lymphoma cells from the two patients showed rearrangements and deletions in immunoglobulin genes with features which cannot be explained by normal immunoglobulin-generating mechanisms and which suggest that the translocations involved these loci at the molecular level. Cloning of the breakpoint using DNA probes from the immunoglobulin genes would prove a novel oncogene at the 3q27 band.