The use of recombinant human erythropoietin (r-HuEPO) in cancer patients improves hemoglobin levels and quality of life. This fact, already well known, made oncologists expect a positive outcome in radio and chemotherapy results, as well as in survival. However, new clinical trials show a preliminary evidence of impaired, instead of improved, survival when these agents are prescribed. Erythropoietin (EPO) is becoming a more complex hormone than it was expected. Its non-erythropoietic effects include, among others, angiogenesis and proliferation of certain types of cancer cells. In this work, we review erythropoietin as a natural hormone, as well as the different types of r-HuEPO, focusing on the confusing situation with regard to their use in oncology. We conclude that extreme care must be taken when EPO is prescribed to cancer patients, and we suggest to limit its use to symptomatic anemia, just to achieve moderate hemoglobin levels.