Pyoderma gangrenosum is a rare cutaneous disorder frequently associated with systemic diseases. The authors report the case of a 28-year-old man with pyoderma gangrenosum and inferior cava vein syndrome due to thrombosis. The search for pyoderma gangrenosum-associated conditions (gastrointestinal, rheumatic, neoplasic, and infectious diseases) was negative. A prolonged partial thromboplastin time and a positive test for circulating anticardiolipin antibodies strongly suggested the diagnosis of the antiphospholipid syndrome. There are reports of at least three other cases of pyoderma gangrenosum associated with the antiphospholipid syndrome. This clinical case adds further evidence to the possible link between these disorders and warrants a search for anticardiolipin antibodies in patients with pyoderma gangrenosum.