A 75-year-old man with a diagnosis of chronic myelomonocytic leukemia evolved with asthenia and worsening cytopenias. A complete blood count showed hemoglobin 9.2 g/dL, neutrophils 0.5 × 10 9/L, monocytes 1.3 × 10 9/L, and platelets 20 × 10 9/L. Peripheral blood smear revealed 35% blast cells with a moderate nuclear:cytoplasmic ratio and one or more nucleoli. A high proportion of blast cells showed a hand-mirror morphology characterized by a cytoplasmic tail extending out from one pole of the nucleus (panels A and B, arrows) and harboring a few azurophilic granules and Auer rods (panels A and B, arrowheads). Bone marrow aspirate revealed 34% blast cells with similar morphology. Flow cytometry analysis confirmed an increased number of myeloblasts (CD34 +, CD117 +, CD13 +, MPO +). Cytogenetic analysis demonstrated 13q deletion in 3 metaphases—46,XY,del(13)(q12q22)[3]/46,XY[17].Hand-mirror cells have been described mostly, but not exclusively, in lymphoid malignancies, especially acute lymphoblastic leukemia, T-cell lymphomas, and multiple myeloma. Nevertheless, cases of acute myeloid leukemia with hand-mirror cells have been described in the literature and are often associated with chromosome 13 anomalies, mainly trisomy/tetrasomy 13. Although more frequently related to lymphoid malignancies, our case shows that hand-mirror morphology can also be observed in acute myeloid leukemia, thus emphasizing the lack of specificity of this finding in the diagnosis of leukemias.