To find a clinical staging system for patients with hairy cell leukemia, 391 patients contributed by 22 centers were analyzed using the proportional hazard survival model. Attention was paid to nonsplenectomized patients to find a staging system to predict the survival length at the time of diagnosis. On the basis of hemoglobin level and spleen size at the time of diagnosis, 3 stages could be distinguished with significantly different prognoses (stages I-III). In addition, we addressed the question of splenectomy to identify those patients who benefit from the operation. Using arbitrary, but clinically relevant, criteria to call the operation beneficial, splenectomy appears to be indicated for patients with large spleens (greater than or equal to 4 cm under costal margin) or with smaller, but palpable, spleens when anemia (Hb less than 12 g/dl) is present. The third question concerned the splenectomized patients. To indicate the patients who have a poor postsplenectomy survival, a staging system was developed on the basis of hemoglobin level and number of neutrophils at 2–3 mo after the operation (stages A-C). The validity of the two staging systems was supported by the results of an analysis of an independent test series of patients. These staging systems may be helpful for the choice of therapy and in the planning of clinical trials in patients with hairy-cell leukemia.