In the case described here, the concomitant presence of PsA and the PBC-PSC overlap syndrome as well as the patient’s good response to TNF-α blockers all seem to confirm a common pathogenesis and point to the hypothesis that the use of anti-TNF-α drugs could be effective in one or more subsets of autoimmune colangiopathies. This evidence concerns the gene TNF and overlapping connective tissue disease.