OBJECTIVES: Epoetin reduces the transfusion rate in cancer patients undergoing chemotherapy, but it has a high cost and a variable response rate. The Anemia Guidelines Development Group recommended to limit its use when before-cycle haemoglobin is <10 g/dL and the expected drop is >1 g/dL/cycle. With the present study we aimed at assessing the propensity to use epoetin in realife practice and its economic implications. METHODS: A retrospective study enrolled 170 cancer patients in 3 Italian centres. Chart review allowed to estimate clinical outcomes and consumption of health care resources within the 3-month study period: the costs were calculated from the perspective of the National Health Care System and transformed to logarithms before analysis. An Epoetin Administration Index (EAI) was calculated through Classification and Regression Trees (CRTs). RESULTS: The population, aged 60.5 years (sd 10.2), was equally distributed among three cancer sites: gastrointestinal, head-neck-lung and ovary. Epoetin was administered to 70% of the patients, but only 5% of them had a pre-chemotherapy haemoglobin <10 g/dL. We thus calculated that epoetin was used inappropriately in 40% of the patients, while it was inappropriately not administered in 65% of the patients who got transfusions, instead. The EAI was higher in patients enrolled by center n°3, those with ovary cancer and with a higher haemoglobin or a higher anemization speed. Accuracy of the propensity score was high (accuracy 93%). The CRT splitted patients based on a haemoglobin cutoff of 9.9 g/dL: more anemic patients had a 1:7 odds to get epoetin, despite the guidelines. Overall cancer care costs €9686 per epoetin-treated patient and €4199 per transfusion-treated patient but the average epoetin-and-transfusion-free costs were very similar in the two groups. The costs varied highly between centres, but a high EAI independently decreased the without-epoetin-costs by 15%. CONCLUSIONS: An appropriate and homogeneous use of epoetin might reduce the costs of cancer treatment.