We present a male patient with polycythemia vera (PV) in whom pyoderma gangrenosum (PG) was induced by subcutaneous injections of interferon-α2beta (IFN-α2b).The patient presented with a 6 cm wide necrotic ulcer on the external aspect of his left thigh, which was surrounded by an erythematous and indurated plaque. He also had a simetrical but smaller 2 cm of size ulcer on the external aspect of the right thigh. Histopathological examination showed a massive perivascular and interstitial inflammatory infiltrate. It was vastly composed of neutrophils and secondary formation of interstitial neutrophilic microabscesses was also observed.To our knowledge only two cases of PG secondary to IFN-α2b injections have been reported, none of them in a patient with PV. Physicians should be aware of these IFN-α2b-related local adverse effects as they might become extremely severe. Immediate local discontinuation of drug administration is mandatory. In order to avoid these complications, alternating injection sites is highly advisable.