When observing Raman images of AML M5a cells, the most evident feature is the presence of a variable extent of carotenoids signals in the cytoplasm, scarcely observed in the AML M0, M1, M2, and M3, and the almost complete absence of MPO. Carotenoid signals (mainly associated with bands around 1156 and 1526 cm -1 ) (Fig. ) may occupy the entire cytoplasmic regions or be more dispersed in specific lipid-rich granules (called "Gall bodies") , with a certain variability among patients. These cells are generally characterized by abundant cytoplasm (i.e., low nuclearcytoplasmic ratio, Fig S6 ) and, in some cases, it is possible to recognize typical nuclear features, including nucleoli and bilobated nuclei (Fig. ). While the nuclear and cytoplasmic features, together with the absence of MPO, are well-known features recognized by hematologists in the so-called M5a monoblasts, the presence of carotenoids is not reported as a typical sign of AML M5a in the current guidelines. This could be due to the lack of methods for the detection of carotenoids by staining or labelling procedures. At the same time, this indication points out an interesting feature that seems to characterize the M5a subtype, at least among the AML subtypes. As of now, no previous literature has reported a correlation between subcellular carotenoid deposits and AML M5a leukemia. This suggests that label-free imaging can not only guide leukemia classification but also offer new fundamental insights into its subtypes.