BACKGROUND: Nucleated red blood cells (NRBCs) are immature erythrocytes. The current line of thought is that increased NRBC production in the immediate neonatal state primarily reflects hypoxic injury and a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis. So, the accurate, reproducible, and timely reporting of NRBC is an important function of the clinical laboratory. The aim of this study is to evaluate the performances of the ADVIA 2120 Hematology System (Siemens, USA) in the NRBCs measurement and compare them with the conventional microscopic method. METHODS: The study was performed in Kangnam Sacred Heart Hospital from March to September, 2009. One hundred twenty neonatal samples were submitted to measure NRBC count. For comparison, 225 blood samples except neonates were also included. The specimens were analyzed for the NRBC counts both with ADVIA 2120 analyzer and by microscopic method. RESULTS: Correlations of NRBC counts form the ADVIA 2120 compared with microscopic results were excellent in neonatal and in all specimens, r=0.8630 and r=0.9012, respectively. Sensitivity and specificity for the presence of NRBC was 98.2% and 94.2%, respectively. Concordance rate was 95.5%. There were some discordant results in cases of chronic lymphocytic leukemia and iron deficient anemia. CONCLUSIONS: The ADVIA 2120 NRBC method correlated well with the manual microscopic method. The automatic correction of the WBC count and differential, the shorter turnaround time compared to microscopic counting are additional advantages of automatic method. The automatic NRBC counting is considered to be a useful method in neonatal hematology.