Interferons are cytokines produced by cells in response to stimulation by certain antigens and infectious agents. In recent years, recombinant interferons have been developed, which have antiviral, antiproliferative, and immunomodulatory functions. Several cutaneous reactions have been reported, including cutaneous ulceration at injection sites. We now report three cases of cutaneous ulceration caused by interferon beta-1b injections. In addition, we review all of the previously reported cases of cutaneous ulceration caused by recombinant interferons and discuss the different mechanisms by which these substances may produce this effect.