Unlike other leukemia types in which the bone marrow findings are diagnostic, the bone marrow pathology of T-cell granular lymphocytic leukemia (GLL) is subtle and ill-defined. In this study, bone marrow biopsy specimens from 36 patients with T-cell GLL and from 25 control patients with cytopenias and relative or absolute increases in blood large granular lymphocytes were studied by immunohistochemistry using antibodies to the cytolytic lymphocyte antigens CD8, CD56, CD57, TIA-1, and granzyme B. The goals were to clarify the bone marrow pathology of T-cell GLL and to refine the diagnostic criteria for T-cell GLL. Most bone marrow specimens from the T-cell GLL patients contained interstitially distributed clusters of at least 8 CD8(+) (83%) or TIA-1(+) (75%) lymphocytes or clusters of at least 6 granzyme B(+) (50%) lymphocytes. Interstitial clusters of CD8(+), TIA-1(+), or granzyme B(+) cells were present in 36%, 12%, and 0%, respectively, of the control bone marrows (all values significantly different, P <.001). An additional T-cell GLL disease-specific finding was the presence of linear arrays of intravascular CD8(+), TIA-1(+), or granzyme B(+) lymphocytes, found in 67% of cases of T-cell GLL and in none of the 25 control samples (P <.001). Staining for CD56 and CD57 was noncontributory. These findings clarify the bone marrow histopathology of T-cell GLL and provide an additional tool by which the discrete, abnormal lymphocyte population required for a diagnosis of T-cell GLL can be identified.