Background: Interferon beta-la and -1b have been increasingly used for the treatment of multiple sclerosis (MS). The most frequent systemic adverse effects are flu-like symptoms. Laboratory abnormalities include asymptomatic leukopenia and elevated hepatic transaminases. Myelodysplastic Syndrome (MDS) refers to a spectrum of hematological disorders which can occur in different situations. Several hematological abnormalities have been reported following interferon therapy.Methods: We report two cases of secondary MDS after long term interferon therapy by using the laboratory data and bone marrow results.Conclusion: Both of our cases were reversible; although treatment with IFNβ-1a and-1b is safe and well tolerated in the majority of population, we should be careful about this premalignant hematological disorder.