The Mindray 6800 Plus analyzer reports red cells (RBC) extended parameters, which represent the subsets of erythrocytes. We aimed to evaluate the reliability of RBC extended parameters in the differential diagnosis of microcytic anemia. The learning set comprised samples from 250 patients with microcytic anemia mean cell volume <80 fL. MH ratio (%microcytic cells/%hypochromic cells) and other discriminant functions were calculated. Optimal cut offs were established using receiver operator curves. This value was used in the validation set of 135 patients 50 carriers and 85 with mild iron deficiency anemia (IDA). Area under the curve 0.945 (95% confidence interval 0.890 to 0.977), cut off >10 rendered the best Youden index (0.798), sensitivity 93.2%, specificity 86.2%. In the validation set using MH ratio >10, 45 in 50 patients were correctly classified as carriers. All of 40 beta carriers were correctly classified, while the 5 false negatives resulted to be alpha carriers. In the IDA group 5 patients had MH ratio >10 and thus considered carriers, but all of them had Hyper <3%. The combination of MH ratio >10 and %Hyper <3% correctly classified 100% of IDA patients. An algorithm derived from RBC extended parameters provided by the Mindray 6800 Plus analyzer could be a useful tool in the differential diagnosis of microcytic anemia.