Hodgkin's disease, especially its biology and pathogenesis, has been under discussion for more than 160 years. Numerous investigations have focused on the nature and clonality of Hodgkin cells, but so far no definitive answer have been yielded by immunohistochemistry, Southern blotting and PCR. However, the use of single-cell PCR has now made it possible to answer the question of the derivation of Hodgkin cells. Using a micromanipulator, Hodgkin cells can be picked out of histological sections and B-cell specific gene rearrangements (VDJ) can be amplified. With this technique it has proved possible to demonstrate the B-cell derivation of Hodgkin cells and their clonality. Mutated immunoglobulin genes in lymphocyte-predominant Hodgkin's disease indicate a germinal center cell origin of Hodgkin cells of this type. These findings, however, do not exclude cases of Hodgkin's disease with Hodgkin cells with a T-cell genotype.