Erythropoietin is a glycoprotein predominantly produced in the kidney. It is an essential regulator of erythropoiesis in the bone marrow. Although cancer-associated anemia is caused by multiple factors, recombinant erythropoietin (rhuEpo) was widely used to treat and prevent this condition. Several clinical studies showed that the use of rhuEpo results in an efficient reduction of red blood cell transfusions in cancer-associated anemia. However, over the past twenty years, Epo and its receptor EpoR were found to be expressed also outside the hematopoietic system and in malignant tumors. This led to a discussion concerning potential risks associated with the application of erythropoiesis-stimulating agents in oncology.