The JAK/STAT signaling pathway connects extracellular ligands with the transcriptional machinery.33 Quantitative aspects of STAT signaling limit the extent and the duration of activation with decisive effects on gene expression influencing neoplasia.13, 27 Here, we describe a new interplay between tyrosine phosphorylation and O-GlcNAcylation of STAT5. Here, STAT5B is linked to neoplasm.