We report a case of a 21-year-old woman with hematopoietic, immunological, and congenital dysmorphic abnormalities, who died following rapidly progressive, disseminated Epstein-Barr virus (EBV)-associated lymphoproliferative disease (LPD). Polymerase chain reaction (PCR) amplification of formalin-fixed paraffin-embedded tissue showed differences in the clonality of each separate lymphoproliferative lesion examined, as determined by immunoglobulin heavy chain (IgH) gene rearrangement. PCR analysis also demonstrated that all lesions contained EBV genome. Since DNA had been extracted from paraffin blocks, a direct comparison of morphology and clonality could be made in each individual lesion. The evidence from this study indicates that the monoclonal tumors arose de novo in multiple sites and that the polyclonal background observed in some lesions reflected a substantial concomitant inflammatory response.