Previous reports have suggested an increased risk of psoriasis in MS patients. Worsening of dermatologic lesions during interferon therapy has been rarely reported, but activation of psoriatic arthritis has not been described until now. The following is a case report. A 37-year-old woman affected by relapsing-remitting multiple sclerosis had severe worsening of cutaneous psoriasis and activation of psoriatic arthritis during interferon beta treatment. The symptoms resolved after therapy discontinuation. This case further supports that activation of psoriasis might be a rare side effect of IFNB therapy and suggests careful evaluation of concomitant morbidity to allow a patient-oriented treatment strategy.