A general overview of Raman images (Fig. and Fig. ) and cluster distribution (Fig. ) allows the description of peculiarities and common features of the two main leukemia types, namely AMLs and ALLs. The group of five AML subtypes studied here (M0, M1, M2, M3, M5a and M6) is characterized by high complexity and high heterogeneity at both morphological and compositional levels, especially if compared to the group of the ALL subtypes (B Ph+, B Ph-, T). This is consistent with the description of leukemia subtypes by current guidelines and with the lineage associated with the two groups. In fact, AML affects the myeloid lineage, mainly responsible for the production of granulocytes, monocytes, and erythrocytes, which are associated with very different cellular functions, such as phagocytosis, bacteria/fungi neutralization, or oxygen transport , all associated with characteristic biochemical features (e.g., metalloproteins), with recognizable Raman features 20 . On the contrary, Raman images belonging to the ALL group show very similar features, generally conserved across the different ALL subtypes. The legend at the top indicates the color and the corresponding subcellular component of each cluster (see Fig. and Fig. ). b) Bar plot showing the same distributions, highlighting the relative cluster frequency for each leukemia subtype (see Supplementary Information for more details). This is also consistent with the biology of the lymphoid lineage, which is responsible for producing only lymphocytes, the cells that mediate humoral immunity, pathogen recognition, and the production of immune mediators (cytokines and antibodies) . These cellular functions are finely regulated and intrinsically complex at the genetic and molecular level but, compared for example to phagocytosis and oxygen transport typical of the myeloid cells, are not associated with subtle biochemical changes, and therefore less visible in the Raman spectrum. In addition, as expected from official classification guidelines 1,2 , cells isolated from ALL subtypes are very similar and can be hardly distinguished by morphological features.