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The present report describes the first recognized case of cytomegalovirus (CMV) colitis following azacitidine therapy. A 66-year-old woman with myelodysplastic syndrome developed CMV colitis, which responded to treatment with ganciclovir. Currently, patients receiving azacitidine do not undergo CMV testing, or receive prophylaxis or CMV-free blood products; however, this policy needs to be revised.