Interaction of IL‐10 with its receptor leads to the activation of STAT transcription factors. Herein we report the IL‐10 dependent simultaneous activation of three STAT transcription factors: Stat1, Stat3, and Stat5. Upon IL‐10 treatment multiple Stat proteins become simultaneously activated, and bind to different promoters with equal kinetics but form distinct homo‐ and heterodimeric transcriptionally active complexes depending on the STAT‐consensus elements of a selected gene promoter. Upon IL‐10 treatment Stat1, 3, and 5 bind to the GRR of the FcγRI gene, activated Stat1, and 3 bind to the SIE sequence of the c‐fos promoter and transcriptionally active Stat5 assembles at the PRL‐STAT consensus sequence of the β‐casein gene. Thus, functionally relevant STAT dimerization is influenced by the activated cytokine receptor as well as the specific STAT consensus sequence present in a specific gene promoter.