SJL mice are an inbred strain of mice with a high incidence of spontaneous lymphomas of B-cell type often involving multiple abdominal organs, and are therefore a useful model for studying the clonal relationship among lymphomas at multiple sites. Thirteen SJL mice with well-developed tumors were killed at a median age of 56 weeks. Autopsy samples were taken from various enlarged lymphoid organs, and the histologic appearance of lymphomas was recorded. Using rearrangements of immunoglobulin genes (heavy and kappa-light chain genes) and integration patterns of murine leukemia virus as clonal markers, 7 of the 13 informative mice showed complete clonal identity among the different sites selected from each mouse; 5 of 13 mice demonstrated at least one shared clonal band with one or more markers being different among the different sites. The histologic appearance of the lymphomas from the various sites was found to be heterogeneous, even when there was clonal identity. These findings suggest that SJL lymphomas in multiple sites within one mouse are usually derived from a single clone but may show development of subclones within a major clonal population, thus supporting the notion that clonal evolution is a common event in the course of development of lymphoid neoplasia.