There is currently no consensus on the best treatment for unresectable hyaline-vascular variant or for multicentric Castleman's disease (MCD), because none of the reported regimens have consistently produced complete response or durable remission in the majority of patients In the present study, we report on the use of 2-CdA (2-chloro-deoxyadenosine) in three patients, two of them with MCD and one with unresectable hyaline-vascular type disease. Relapse-free survival of the responding patients was 24 and 20 months. Later, both patients evolved to non-Hodgkin's lymphoma (NHL) (diffuse large B-cell lymphoma and peripheral T-cell NHL, respectively). 2-CdA typically causes a long-lasting state of immunodeficiency and the profound influence of this drug on the immune system has raised questions concerning the emergence of secondary neoplasms after its use. Therefore, it is reasonable to conclude that: 1) 2-CdA can induce durable complete remission in MCD patients but unfortunately it cannot cure the disease; 2) the possibility that 2-CdA may accelerate the transformation of MCD to NHL cannot be ruled out.