Pyoderma gangrenosum (PG) is a rare, noninfectious, neutrophilic dermatosis of unknown origin that is associated with systemic diseases in 50% of cases. The authors present a case of a 54-year-old man patient with refractory to conventional treatment PG associated with ulcerative colitis and psoriasis, which showed a successful response to treatment with infliximab, a chimeric monoclonal antibody that inhibits tumor necrosis factor alpha (TNF-α). This case report shows the frequent difficulty in the therapeutic approach of PG, especially if associated with underlying disease, and necessity to apply new agents, such as a novel application of the TNF-α inhibitors, in relationship to the recent pathogenic knowledge.