We report two cases of myelodysplastic syndrome (MDS) with del(5q) isolated cytogenetic abnormality in elderly patients: AREB-1 in Patient 1, "5q syndrome" in Patient 2. A first line of treatment including hematopoietic growth factors (darbepoetin alone or associated with G-CSF) failed after several months and a treatment with lenalidomide was initiated in both cases. The treatment was poorly tolerated (myelosuppression) in Patient 1 without an improvement of the quality of life; a progression of the disease was observed with an increase of the bone marrow blastosis and a new acquired karyotypic abnormality (t13;17), leading to the prescription of 5-azacytidine. Patient 2 had a good response to lenalidomide for several months with an increase in the haemoglobin level and a transfusion independence. The patient's prognosis suddenly worsened with the occurrence of a blood blastosis (10%): 5-azacytidine was thus initiated. These two case reports illustrate the recent advances in the management of patients with MDS with del(5q), including the use of lenalidomide.