Signal transducers and activators of transcription (STAT) are a family of transcription factors that regulate a broad range of cellular processes, such as proliferation, differentiation, and survival, in a large variety of cell types. Because of their regulation of diverse cellular functions, their aberrant activation is frequently associated with disease development, particularly oncogenic diseases. Much evidence exists to suggest that STAT proteins play a significant role in cellular transformation. However, which STAT proteins and to what extent they cause transformation and subsequent disease progression are topics currently being investigated. In this review, we will report on the findings concerning the involvement of Stat6 in the development of lymphoma and leukemia. Mounting evidence, in both patients and mouse models, supports a model where Stat6 is not a mere bystander, but rather, plays an active role in promoting a transformed phenotype.