The monitoring of diabetic patients by evaluating glycated protein levels is now widely accepted and performed. The microchromatographic version of the high performance liquid chromatography method is the technique most frequently used in clinical practice. The DCA 2000 instrument (Bayer Diagnostics, Milan, Italy), based on an immunochemical technique, has been proposed for the rapid and simple evaluation of HbAlc, using even capillary blood. We evaluated 171 subjects including 22 healthy volunteers, 78 type 2 diabetic patients with different degrees of metabolic control, 11 women affected by gestational diabetes mellitus (GDM), 6 patients with hyperlipemia, 38 patients with chronic renal failure, 13 diabetic patients with chronic renal failure, and 3 patients with hemoglobinopathies. The DCA 2000 model was compared with the Diamat HPLC system. Data from within-run imprecision studies showed excellent precision, for both DCA 2000 and the HPLC system. The correlation between the two different systems, as shown by other statistical evaluations, was good (y = 0.911x + 0.462, r = 0.923). Results from the control group and diabetic patients were used to compare the two methods. Values obtained using the DCA 2000 were significantly lower (p < 0.0001) than those obtained with the HPLC system, in both healthy subjects and diabetic patients. To detect possible interferences, selected samples were analyzed from patients with hyperlipemia, diabetes and chronic renal failure, and hemoglobinopathies. While in the case of hyperlipemia, an acceptable correlation coefficient between the two systems was confirmed (y = 1.047x - 1.236, r = 0.876), in the case of chronic renal failure the correlation turned out to be very low (y = 0.254x + 3.456, r = 0.203). Our results indicate that the DCA 2000 gives accurate and reliable results in the clinical field of interest.