Large granular lymphocytic (LGL) leukemia is an uncommon, usually indolent, lymphoproliferative disorder strongly associated with various autoimmune diseases. The authors report a case of a 67-year-old woman with a long-standing rheumatoid arthritis, who developed neutropenia and associated recurrent infections, diagnosed with LGL leukemia. We describe the treatment approach and the response to an anti-TNF and the rituximab.