ABSTRACT: Anemia resulting from cancer, or its treatment, is an important clinical problem increasingly treated with the recombinant hematopoietic growth factor erythropoietin. To address uncertainties regarding indications and efficacy, the American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. The guideline panel found good evidence to recommend use of epoetin as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin level less than 10 g/dL. Use of epoetin for patients with less severe anemia (hemoglobin < 12 g/dL but never below 10 g/dL) should be determined by clinical circumstances. Good evidence from clinical trials supports the use of subcutaneous epoetin thrice weekly (150 U/kg tiw) for a minimum of 4 weeks. Less strong evidence supports an alternative weekly (40,000 U/wk) dosing regimen, based on common clinical practice. With either administration schedule, dose escalation should be considered for those not responding to the initial dose. In the absence of response, continuing epoetin beyond 6 to 8 weeks does not appear to be beneficial. Epoetin should be titrated once the hemoglobin concentration reaches 12 g/dL. Evidence from one randomized controlled trial supports use of epoetin for patients with anemia associated with low-risk myelodysplasia not receiving chemotherapy; however, there are no published high-quality studies to support its use for anemia in other hematologic malignancies in the absence of chemotherapy. Therefore, for anemic patients with hematologic malignancies, it is recommended that physicians initiate conventional therapy and observe hematologic response before considering use of epoetin.