Basing on the current data, it seems reasonable in CRMO setting (i) to withdraw the anti-TNF agent if PG or PG-like pustular eruptions appear following the newly introduced therapy (especially within the first 6 months of treatment), (ii) administer a cycle of conventional immunosuppressants (corticosteroids and/or cyclosporine) and (iii) consider to switch the TNF inhibitor with another effective biologic agent. The gene discussed is TNF; the disease is chronic recurrent multifocal osteomyelitis.