The association of hairy cell leukemia (HCL) with other neoplasms, mainly non-Hodgkin's lymphomas, is well known. However, the simultaneous diagnosis of HCL and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare, with only few cases of such an association having been reported. We describe three patients with a well-characterized HCL in whom a CLL/SLL population was detected. Of note, these cases represent a significant proportion (11.5%; 95% CI: 0% to 24%) of the total number of HCL cases diagnosed in our institution during the same period of time. All three patients were treated with deoxycoformycin. They achieved a complete response of the HCL, whereas the CLL/SLL population persisted in all cases. The immunoglobulin gene rearrangement analysis, in two informative cases, suggested that the HCL and CLL/SLL populations arose from different B cell clones. This study indicates that the association of HCL and CLL/SLL might be much more frequent than previously recognized. Therefore, a large panel of monoclonal antibodies, including those necessary to detect CLL/SLL, should be employed when studying patients with HCL.