In this study we reviewed the morphologic features of marrow biopsies and aspirates as well as splenic sections derived from 28 patients with hairy cell leukemia. Marrow biopsies proved reliable in establishing and/or confirming the diagnosis in every patient, when available for review. Regardless of the degree of marrow involvement, the hairy cell infiltrates consistently exhibited wide spacing of their nuclei due to relatively abundant pale to clear cytoplasm. Hairy cells appeared homogeneous and bland, without mitotic activity or prominent nucleoli; nuclear contours characteristically were ovoid and to a lesser extent slightly indented or reniform. The splenic histology of hairy cell leukemia was equally distinctive. The splenic red pulp was diffusely infiltrated by a uniform population of cytologically monotonous mononuclear cells that expanded the red pulp cords, filled the sinuses, and generally led to atrophy or obliteration of the white pulp. Moreover, the clear cytoplasm of hairy cells usually was highlighted in sinusoidal blood-filled lakes. Despite the employment of these characteristic morphologic criteria for the diagnosis of hairy cell leukemia in marrow and spleen, these pathologic changes may vary and may be simulated in part by a variety of other hematologic disorders. Accuracy of diagnosis requires not only knowledge of the usual pathologic features of hairy cell leukemia but also knowledge of the unusual. Awareness of these pathologic variations will aid in the improvement of diagnosis and will provide a foundation for understanding the clinical and biologic aspects of hairy cell leukemia.