Published in 2008, by experts of the World Health Organization, the new classification of hematological malignancies forced a change of look at chromosomal aberrations and gene mutations, which are important in establishing the diagnosis and prognosis for patients with these malignancies. The new classification includes a new category of neoplasms - hematological malignancies with hypereosinophilia. Due to the high diversity of causes of hypereosinophilia and underlying genetic changes, their differential diagnosis is based on classical cytogenetics, fluorescence in situ hybridization (FISH) and genetic molecular techniques. Cytogenetic analysis of bone marrow cells showed that the majority of hypereosinophilia cases can be characterized by the presence of normal karyotype. Therefore, routine cytogenetic diagnostics should be complemented by FISH with break-apart probes for potentially rearranged genes (e.g., CBFB, ETV6) and unique probes for fusion genes (e.g., FIP1L1-PDGFRA), specific for hypereosinophilia-associated diseases. In differential diagnosis of hypereosinophilia, the analysis of characteristic gene mutations (e.g., cKIT) and gene fusions (e.g., ETV6-PDGFRB) is also applied, using molecular genetic methods.