It is generally accepted that similar molecules exert their inhibitory activity (or biological activity) at a certain site by binding to it in a similar form. Previous results comparing the docking results with those obtained from formal methods relating electronic structure with activity show that there is some equivalence between them. Here we present the results of the docking of twenty two benzenesulfonamides and tetrafluoro-benzenesulfonamides derivatives to the human carbonic anhydrase isoform II. It is shown for the first time that similar molecules do not necessarily bind in the same form to produce an inhibitory action. The docking results are analyzed from the point of view of the ligand-residue distance, kind of residues involved and kinds of weak and short-range interactions. The results suggest that a formal study of a group of molecules should begin by docking them to their action site. If no structure of the site is available then the results of formal methods using linear multiple regression analysis should be carefully examined to detect and discard any molecule presenting a different mode of binding to the site.