Myelofibrosis with myeloid metaplasia (MMM) is a clonal disorder involving disregulation of angiogenesis and immunomodulatory mechanisms. Thalidomide (Thal) retains antiangiogenic, immunomodulatory and cytokine regulatory properties and recently it has been used successfully in multiple myeloma. Here, we report our experience in 10 MMM patients treated with Thal. Patients with agnogenic MMM treated in an early phase of the disease obtained significant benefits from the therapy and remain transfusion-free. In contrast, all secondary MMM failed to respond. These preliminary findings confirm that Thal plays a role in MMM therapy, although the efficacy in the different phases of the disease must be further evaluated.