Background. Patients in the accelerated or blastic phases of chronic myelogenous leukemia (CML) often have painful splenomegaly and secondary thrombocytopenia. We tested the hypothesis that splenectomy can be performed with minimal complications in advanced CML, thereby alleviating pain, reversing thrombocytopenia, and minimizing transfusion requirements. Methods. We reviewed the records of 53 patients in the accelerated or blastic phases of CML who undo went splenectomy between 1970 and 1995 at the U. T. M. D. Anderson Cancer Center. Results. Twenty-eight patients were in accelerated phase and 25 in blastic phase at the time of splenectomy. The most common indications for splenectomy were symptomatic splenomegaly (median splenic weight, 1000 gm; range, 120 to 6700 gm) or thrombocytopenia (platelet count less than 100,000/μl) or both. There was 1 death within 30 days of splenectomy. The preoperative platelet count increased 3. 72-fold ± 0.53- fold (mean ± SEM) by postoperative day 7 (p < 0.001; paired t test). Patients with transfusion-dependent thrombocytopenia had significantly fewer platelet and red blood cell transfusions in the 6 months after splenectomy than in the 6 months before splenectomy (p = 0.016; sign test). Conclusions. Splenectomy can be performed with minimal morbidity and mortality in advanced CML, thereby relieving symptomatic splenomegaly, reversing thrombocytopenia, and minimizing transfusion requirements.