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Sixty per cent of oncologic patients need radiation therapy for cure or palliation. In fact, in most neoplastic diseases, a better local control positively impacts on disease-free survival and overall survival. The efficacy of radiotherapy depends on several factors: while some are tumor-related, others are host-related. Radiobiological phenomena are also important: ionizing radiation is responsible for cell damage (double rupture of DNA chains), mostly an indirect mechanism with the formation of free radicals. Their toxic action is enhanced by the oxygen partial pressure at the cellular level. A number of studies have confirmed that good tissue oxygenation is a function of a high hemoglobin level in the peripheral blood (Hb > or = 13 g/dL). Unfortunately, these values are rarely present in oncologic patients due to the disease-related toxicosis as well as to the therapy induced hematologic toxicity. The treatment of anemia is free of risk for the recent developments in technology which with gene cloning and the technique of recombinant DNA has allowed the production of human recombinant erythropoietin. Erythropoietin is produced by the interstitial cells of renal tubules in response to hypoxia. It prevents apoptosis and promotes erythroid proliferation and differentiation with consequent reticulocyte release and hemoglobin synthesis. It is not completely understood whether the efficacy of radiotherapy depends on hemoglobin values present at the start of irradiation (often less than 12-13 g/dL) or on the higher ones observed during and at the end of radiotherapy. Therefore, preventive systemic erythropoietin therapy in non anemic patients in terms of costs/benefits is at present non sustainable. To the contrary, in patients undergoing radiotherapy to extended fields or aggressive multimodal treatments, for the higher risk of anemia, the early use of this treatment can be hypothesized in case of initial anemia to improve therapy compliance and prevent negative conditioning of results. Keeping in mind that grade 1 minimum toxicity for red cells, according to the Radiation Therapy Oncology Group (RTOG) is equal to 11 gHb/dL we think that this value can be considered as cutoff to start erythropoietin therapy.