WHO criteria for the differential diagnosis of chronic myeloid neoplasms (MPN) to provide for the use from 2008 as the main diagnostic markers of the presence of somatic mutations in the JAK2 gene, CALR, MPL and the results of a bone marrow biopsy. The feasibility assessment of erythropoietin (EPO) levels to distinguish the secondary (reactive) or clonal polycythemia in terms of availability of molecular genetic testing requires additional clarification. Purpose — the comparative assessment of diagnostic and cost-effectiveness using of EPO test as the first algorithm test, or test after receiving the molecular genetic results. The study was performed in venous blood samples of patients with suspected MPN. To identify mutations in JAK2 gene, CALR, MPL was used «in house» allele-specific polymerase chain reaction in real time. Determining the level of EPO was performed in serum using Biomerica EPO ELISA kits (USA) and erythropoietin-ELISA-ABTS kits («Vector-Best», Russia) in the blood plasma. It was shown that elevated levels of EPO does not exclude the presence of JAK2 V617F mutation and if its use as a primary test discriminating results in 10% of false negative results may be detecting. An alternative algorithm with a primary somatic mutations tests reveals more cases of clonal diseases, reduce the time of diagnosis and reduce the cost of identifying a single case of MPN. The negative result of the genetic testing in combination with high or normal levels of EPO is more typical for reactive states and can be recommended for these patients to deferred trepan biopsy.