We performed single cell polymerase chain reaction (PCR) amplification of the t (14 ; 18) translocation from paraffin embedded sections in a case of follicular lymphoma (FL) with subsequent development of Hodgkin lymphoma (HL). The lymphoma cells of FL were positive for CD20, CD10 and BCL-2, and negative for CD3, CD30 and CD15. Hodgkin and Reed-Sternberg (HRS) cells of HL were positive for CD20, CD30 and CD15, and negative for CD3 and CD10. EBER-1 RNA in situ hybridization failed to stain with both lymphomas. HRS cells manipulated and FL cells micro-shaved from individual neoplastic follicles were subjected to single-cell PCR. The t (14 ; 18) translocation, a chimeric DNA containing portions of the bcl-2 and the immunoglobulin heavy chain (IgH) genes, was amplified from four of 27 isolated HRS cells and two individual FL follicles. All t (14 ; 18) PCRs yielded products of the same size, and an identical nucleotide sequence including the t (14 ; 18) translocation was found in both FL and HRS samples. Thus, the data demonstrate the common clonal origin of FL cells and HRS cells in subsequent HL, and that both FL and HL were derived from germinal center B cells with the t (14 ; 18) translocation.