Tyrosine sulfation of proteins is an important post-translational modification shown to play a role in many membrane associated or extracellular processes such as virus entry, blood clotting, antibody mediated immune response, inflammation and egg fecundation. The sole two human enzymes that transfer sulfate moieties from 3’-phospho-adenosine-5’-phospho-sulfate (PAPS) onto tyrosine residues, TPST1 and TPST2, are anchored to the membranes of the trans-Golgi compartment with the catalytic domain oriented to the lumen. In contrast to the relatively well studied organization of medial Golgi enzymes, the organization of trans-Golgi transferases remains elusive. Although TPSTs are known to form homodimers in the Golgi membranes this organization level may represent only a small piece of a puzzle that is linked to the entire picture. Here we report the formation of TPST1/TPST2 heterodimers and a novel interaction between either TPST1 or TPST2 and the α-2,6-sialyltransferase, that indicate a higher organization level of tyrosylprotein sulfotransferases that may serve for substrate selectivity and/or effective organization of multiple posttranslational modification of proteins.