Hairy cell leukemia (HCL) has been reported to sometimes express CD10. However, the reported frequencies have been quite variable and the significance of CD10 expression has not been addressed. Cases of HCL submitted to our flow cytometry service during a 2-year period were evaluated for CD10 expression. Information regarding demographics, clinical manifestations, tissue morphologic features, and response to treatment was reviewed. Of the 97 HCL cases identified, 10 expressed CD10. The level of CD10 staining was typically well above control levels and also could be detected easily by immunohistochemical analysis. All cases analyzed were negative for bcl-6. Our study suggests that approximately 10% of otherwise typical cases of HCL show aberrant CD10 expression. CD10+ HCL cases seem to be morphologically and clinically similar to CD10– HCL cases. Appreciating that HCL can express CD10 may be especially important when evaluating specimens with suboptimal morphologic features and/or limited immunophenotyping panels.