In the present paper a case of a 65-year-old man diagnosed as suffering from a lymphoplasmacytic lymphoma, resistant to conventional chemotherapy, associated to a bone marrow (BM) mastocytosis, who was successfully treated with cladribine is reported. In this patient cladribine induced not only clinical remission of the lymphoplasmacytic lymphoma but it was also associated with immunophenotypical changes in the BM mast cells (MCs) compartment. Such changes were consistent with a decrease in the number of phenotypically aberrant (CD2+/CD25++/CD35++/CD69++/CD117++) MCs and the reappearance in the BM of MCs displaying a normal phenotype (CD2-/CD25-/CD35-/CD69+/CD117+++). Despite the potential utility of cladribine in the treatment of mastocytosis, our observations should be considered as preliminary and caution should be taken as regards the exact indications of the use of this purine analog in mastocytosis.