Ixazomib, a proteasome inhibitor commonly used for the treatment of multiple myeloma, is a rare cause of Sweet's syndrome. We present a 62-year-old man who developed drug-induced Sweet's syndrome during his fifth cycle of ixazomib for treatment of refractory multiple myeloma. Monthly rechallenge led to the recurrence of symptoms. The patient was successfully treated with addition of weekly corticosteroids and resumed his cancer treatment.