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Introduction: the increase of Mean Corpuscolar Hemoglobin Concentration (MCHC) in the Complete Blood Count (CBC) test is a complex issue, deserving great attention. Erytrocytes (RBC) count by impedance and the photometric hemoglobin (HGB) measurement can be influenced by both biological variables (cold agglutinins, lipemia, icterus, hemolysis, RBC alterations) and pre-analytical factors (collection, storage and transport of the sample). In this paper, the Complete Blood Count-Optical (CBC-O) algorithm is evaluated for the identification of the cause of the MCHC increase and for the suggested corrective action to correctly report the CBC parameters. Methods: 255 samples, collected with K2-EDTA anticoagulant, for the CBC test were used. The algorithm was triggered after the reticulocytes reflex testing (XN-RET) using the XN hematology analyzer (Sysmex), when MCHC was >365 g/L. The CBC-O tool uses a number of RBC and HGB measures and indices. Results: the samples were classified by the CBC-O algorithm into 5 groups according to the causes of the MCHC increase: cold agglutinins (n=70), cold agglutinins and HGB interferences (n=10), HGB interferences (n=6), RBC pathologies or hemolysis (n=32) and unclear situations with normal RBC profile (n=137). Discussion: MCHC elevation is a rare occurrence in routine daily practice, but it needs to be managed properly. The CBC-O algorithm is a useful tool since, in a short time, it allows to give indications on the probable causes of the increase and to report correct erythrocyte indices, without the need to treat the sample, which would otherwise lengthen the turn around time. [ABSTRACT FROM AUTHOR]