Hairy cell leukemia (HCL) variant is a rare low-grade B-cell disorder affecting the elderly or middle-aged population with features intermediate between those of HCL and prolymphocytic leukemia. Unlike HCL, it is resistant to most conventional treatment. We report a case of a 53-year-old man who had refractory thrombocytopenia and lymphocytosis for 8 years. Investigations and analysis of spleen and bone marrow revealed a diagnosis of HCL variant. He opted for treatment with rituximab, a chimeric monoclonal antibody targeting CD 20. There was complete recovery of his full blood count and a bone marrow biopsy performed 3 months post-treatment showed complete remission. This is, to our knowledge, the first reported patient with HCL variant for whom treatment with rituximab was successful, and this treatment needs further investigation.