PURPOSE: The purpose of this study was to find out the clinical characteristics and to establish the diagnostic work-up of anemia of chronic disease (ACD) according to the underlying causes in children. METHODS: The medical records of 42 patients with ACD, admitted to the Department of Pediatrics, Wonju College of Medicine from Jan. 2003 to May 2005, were analyzed retrospectively. RESULTS: The underlying causes of ACD were autoimmune diseases (6 patients), cancers (7 patients), and infectious diseases (29 patients). Compared with infections, hemoglobin was significantly lower, and white blood cell, lymphocyte and ferritin were significantly higher in cancer patients. Compared with infections, hemoglobin and MCH were significantly lower, and MCV and ferritin were significantly higher in autoimmune diseases. Likewise, compared with autoimmune diseases, MCV was significantly higher in cancer. Receiver operation characteristic (ROC) curve analysis revealed that ferritin can discriminate infectious causes from autoimmune or malignant causes on the cut-off value of 300 microgram/L with sensitivity of 0.85 and specificity of 0.97. CONCLUSION: When ferritin level is higher than 300 microgram/L, the most likely cause of ACD can be either autoimmune diseases or cancers. Cancers and autoimmune diseases may also be discriminated by MCV, WBC or lymphocyte count.