The objective of the study was to evaluate the diagnostic efficiency of laboratory tests, including serum transferrin receptor (TfR) measurements, in the diagnosis of iron depletion. The patient population consisted of 129 consecutive anemic patients at the University Hospital of Turku who were given a bone marrow examination. Of these patients, 48 had iron deficiency anemia (IDA), 64 anemia of chronic disease (ACD), and 17 patients had depleted iron stores and an infectious or an inflammatory condition (COMBI). Depletion of iron stores was defined as a complete absence of stainable iron in the bone marrow examination. Serum TfR concentrations were elevated in the vast majority of the IDA and COMBI patients, while in the ACD patients, the levels were within the reference limits reported earlier for healthy subjects. TfR measurement thus provided a reliable diagnosis of iron deficiency anemia (AUC(ROC) 0.98). Serum ferritin measurement also distinguished between IDA patients and ACD patients. However, the optimal decision limit for evaluation of ferritin measurements was considerably above the conventional lower reference limits, complicating the interpretation of this parameter. Calculation of the ratio TfR/log ferritin (TfR-F Index) is a way of combining TfR and ferritin results. This ratio provided an outstanding parameter for the identification of patients with depleted iron stores (AUC(ROC) 1.00). In anemic patients, TfR measurement is a valuable noninvasive tool for the diagnosis of iron depletion, and offers an attractive alternative to more conventional laboratory tests in the detection of depleted iron stores.