A 40 year-old man with hairy cell leukemia (HCL) was treated with Cladribin, but achieved only partial response (PR). As expected, both 2 and 5 years later the disease had progressed and the patient was therefore twice retreated with Cladribin. A bone marrow examination after the last Cladribin course showed complete response with residual disease (CR-RD). The patient received consolidation therapy with Rituximab, achieved complete response (CR) and was still in CR 9 months later. Rituximab is a good treatment option for patients with refractory HCL because of its significant activity and minimal toxicity.