Rituximab use in B-cell malignancies has been widely favored by the acceptable toxicity profile of this drug. Episodes of rituximab-induced neutropenia have been reported in some patients, but severe acute thrombocytopenia is very unusual. Here, we report transient severe acute thrombocytopenia after rituximab infusion in two patients with, one hairy cell leukemia the other with mantle cell lymphomay. Interestingly, in both cases, thrombocytopenia was reversible in a few days without further therapeutic intervention. The mechanism of this side effect remains unclear. Previous reports suggested the presence of CD20 antigen on the platelets themselves or that soluble CD20 antigen in the circulation may cause an antigen-antibody reaction and immune-mediated cell lysis. It is noteworthy that the two cases reported here as well as the two previously published cases share massive bone marrow involvement by neoplastic B lymphocytes.