We measured T-cell intracellular antigen-1 (TIA-1) expression in neoplastic cells from patients with hairy cell leukemia. Five of nine cases were positive for cytoplasmic TIA-1, with a small, dot-like, granular expression pattern. However, neoplastic cells were granzyme B- and perforin- negative in all cases. Other positive markers were CD20 in 9/9 cases, CD19 in 9/9 cases, DBA44 in 8/9 cases, LeuM5(CD11C) in 8/9 cases, IL-2R(CD25) in 7/9 cases, CD103 in 7/9 cases, FMC7 in 6/9 cases, and tartrate- resistant acid phosphatase in 5/7 cases. We also analyzed TIA-1 expression in 94 B cell lymphomas, including 19 diffuse, large cell lymphomas, 19 mantle cell lymphomas, six follicular lymphomas, two extranodal marginal zone B-cell lymphomas, 13 nodal marginal zone B-cell lymphomas, one mediastinal large-cell lymphoma, 19 diffuse small-cell lymphomas, 14 myelomas, and one splenic lymphoma with villous lymphocytes. All cases were negative for TIA-1 expression. Based on these findings, TIA-1 expression in neoplastic cells of low-grade B-cell lymphomas may be a good diagnostic marker for hairy cell leukemia. Moreover, TIA-1 reactivity in lymphomas does not necessarily indicate a T- or NK-cell derivation.