The PDGFRB (platelet derived growth factor receptor beta) gene encodes a transmembrane glycoprotein that belongs to the type III receptor tyrosine kinase family and has a key role in a variety of cellular processes. Translocations involving the PDGFRB gene are rare genetic disorders and are identified in myelodysplastic/myeloproliferative neoplasms (MDS/MPNs), chronic myeloproliferative disorders (CMPD), acute myeloid leukemia (AML), and also in atypical (BCR-ABL1-negative) chronic myeloid leukemia/chronic myelomonocytic leukemia (CML/CMML)-like diseases, often with eosinophilia and splenomegaly. The most common translocation involving PDGFRB is the t(5;12)(q32;p13.2). Result of this translocation is the fusion protein ETV6-PDGFRB, in which the pointed domain of ETV6 is juxtaposed next to the transmembrane and entire tyrosine kinase domain of PDGFRB. As a result, the tyrosine kinase is constitutively activated leading to hematopoietic cell proliferation. Patients with PDGFRB translocations respond well to imatinib therapy with excellent hematopoietic and molecular responses. Recent studies revealed that sorafenib is a further potential inhibitor of patients with ETV6-PDGFRB translocation.