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Anemia is a major cause of morbidity in cancer. Erythropoiesis stimulating agents (ESA) are a mainstay of treatment, although some patients lack response for unknown reasons. Recently, ESA dosing recommendations have changed and iron is increasingly used as an adjunct. Due to these changes, potential laboratory predictors of response were re-evaluated.This was a multi-center, observational study in cancer outpatients developing anemia under standard chemotherapy without absolute iron deficiency. For up to 12 weeks, laboratory data was collected while patients were treated with darbepoetin α (DA) either alone or along with intravenous iron. Baseline erythropoietin (Epo), changes in soluble transferrin receptor (sTfR) and in hemoglobin (Hb) early after treatment initiation were re-evaluated as response predictors, based on logistic regression models.Overall, 279 patients (mean age 66.1 years, 59.5% female) entered the study; 171 (61%) received at least one iron dose along with DA. Response and its predictability hardly increased through adjunct iron, although baseline ferritin <100 mg/L resulted in a 10 times higher probability of response to the combination than to ESA alone. Baseline Epo had low predictive value, regardless of tumor type or use of adjunct iron, although it varied with sex and age. If criteria for all three - Epo, sTfR, and Hb - were met, probability of preventing transfusions was 97%, dropping to 44%, if all three failed.Changes in ESA treatment recommendations had no impact on the predictability of response. Best prediction is still based on the immediacy of Hb increase.