This chapter presents a state of the art summary of myeloid/lymphoid neoplasms with eosinophilia and rearrangement to its definition, biology, epidemiology, disease mechanisms, clinical signs, diagnosis, treatment and prognosis. Myeloid/lymphoid neoplasms with eosinophilia and rearrangement are further separated into: myeloid/lymphoid neoplasms with platelet-derived growth factor receptor beta (PDGFRA) rearrangement, myeloid/lymphoid neoplasms with PDGFRB rearrangement, myeloid/lymphoid neoplasms with FGFR1 rearrangement, and provisional entity—myeloid/lymphoid neoplasms with PCM1-JAK2 rearrangement. Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1, or PCM1-JAK2 are rare, with an age-adjusted incidence rate of 0.036 per 100,000. Diagnosis of eosinophilia-associated neoplasms involves blood count/morphology, serum chemistry, bone marrow morphology/immunohistochemistry, flow cytometry of myeloid, B- and/or T-lymphocyte markers, and molecular analysis of gene fusions. Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA or PDGFRB show excellent response rates to imatinib mesylate and imatinib treatment for complete and durable hematologic and complete molecular remissions.