The nucleoporin NUP98, a component of the nuclear pore complex, is involved in nucleocytoplasmic transport and exhibits multiple roles in RNA export from and protein import into the nucleus. Rearrangements of the NUP98 gene have been implicated in the pathogenesis of several types of hematologic malignancies, including de novo and therapy-related acute myeloid leukaemia (AML), and also myelodysplastic syndrome (MDS), chronic myelogenous leukaemia (CML), and T-cell acute lymphoblastic leukaemia (T-ALL). NUP98 rearrangements result in the fusion of the N-terminal region of NUP98, which is rich in phenylalanine-glycine (FG) repeats, to one of 29 different proteins. Many of the NUP98 fusion partners are transcription factors of the homeobox family. NUP98 fusions cause aberrant differentiation and increased proliferation when expressed in primary human hematopoietic cells. Malignancies with NUP98 rearrangements are associated with a poor prognosis and a poor treatment outcome indicating the usefulness of NUP98 as a prognostic biomarker.