Although flu-like symptoms are the most common side effect associated with alpha interferon therapy, cutaneous reactions also can occur and present a management challenge for oncology nurses. Cutaneous reactions reported in the literature include generalized effects and localized reactions. Alopecia appears to be the most common generalized cutaneous reaction reported, followed by transient and mild generalized rash-like reactions. Localized manifestations include injection-site reactions, induration, or necrosis. Armed with knowledge about interferon-associated cutaneous reactions, oncology nurses can identify these reactions early and promptly implement appropriate interventions.