Tumor cells from 15 canine lymphoma/leukemia cases were examined for genetic rearrangements of immunoglobulin and T-cell receptor (TCR) genes in parallel with cell surface antigens. Ten of these 15 cases showed rearrangements of the immunoglobulin heavy chain (IgH) gene, while 4 cases displayed TCR beta-chain gene rearrangements on Southern blot analysis. All the cases with IgH gene rearrangements had multicentric form lymphoma, and 6 of the 10 cases were cell surface immunoglobulin-positive. On the other hand, the cases with TCR gene rearrangements included atypical lymphoma/leukemia cases, and 3 of the 4 cases were Thy-1 antigen-positive. Although the tumor cell lineage of a considerable number of lymphoma/leukemia cases could not be determined by phenotypic analysis, examination of the IgH and TCR gene rearrangements disclosed the lineages of 14 of 15 cases. Genetic analysis demonstrated that the tumor cells in most canine multicentric lymphomas were formed by clonal expansion of B-lymphocyte. These findings show that studies on the rearrangements of immunoglobulin and TCR genes are very useful for understanding the cellular origin, clonality and hierarchy of canine lymphoma/leukemia cells.