Classical Hodgkin's lymphoma (cHL) and B-cell Non-Hodgkin Lymphoma (B-NHL) occasionally occur in the same patient. However, molecular studies that aim at determining the clonal relationship between both lymphomas are rare. In most instances, the lymphoma components appear to be derived from the same germinal center (GC) B cell precursor. We describe the molecular monitoring of repeated clonal relapses in a patient with cHL in whom diffuse large B cell NHL (DLBCL) developed concurrently. Intriguingly, both lymphomas were clonally unrelated. Thus, the derivation from a shared precursor likely is not a general rule in cHL and DLBCL arising in the same patient.