Various studies reported the use of Raman approaches for the study of leukemia but only part of them included patients' samples . Chan et al. and Managò et al. reported the characterization of leukemia cells derived from ALL patients . Féré et al. and Happilon et al. reported an extended study on smears from 79 chronic lymphocytic leukemia (CLL) patients demonstrating good accuracy in discriminating leukemia cells . However, the abovementioned studies are based on single-point measurements, most of the time collecting Raman signals from the nucleus. This approach has some advantages, including simplicity and reduced acquisition time, but fails to provide morphological and spatial information, and does not provide details about the biomolecular features of cellular cytoplasm, containing key information about cell phenotypes. In addition, the abovementioned Raman studies do not include patients affected by AML, characterized by high biomolecular heterogeneity.