AML M6 cells studied by Raman imaging approaches reveal very strong HB signals, diffused over the entire cellular volume and characterized by very sharp and very specific preresonance Raman features (mainly around 665, 752, 1545, and 1610 cm -1 ) 20,51 (Fig. ), all associated with the heme group (porphyrin). The presence of HB agrees with classification guidelines reporting the predominance of erythroid precursors (erythroblasts) in patients' samples . At the same time, even if the preponderance of hemoglobin prevents nuclear pixels from being automatically assigned to nuclear clusters (#4 -7) the shape of the nucleus can be recognized in some AML M6 cells, described by cluster #15, and also DNA signals (788 cm -1 ) are visible at spectral level (Fig. ). For instance, the nuclear presence is in agreement with the description of erythroid precursors in AML M6 . Concerning ALL subtypes, the cluster analysis produced similar Raman images for all three subtypes (ALL B Ph+ , ALL B Ph-, ALL T) with a certain degree of variability among cells and, even more pronounced, among patients. In general, most of ALL cells (lymphoblasts) revealed a high nuclearcytoplasmic ratio (Fig. )-like what was observed in AML M0 cells-and the complete absence of MPO. This agrees with the definition of ALL subtypes, belonging to the lymphoid lineage and lacking MPO production . At the same time, some cells, especially those belonging to specific patients, showed carotenoids signals, like what was observed in AML M5a cells, but generally less abundant. As observed for AML M5a cells, also in the case of ALL subtypes, the presence of carotenoids and their correlation with leukemia is not reported in the current guidelines. What is clear from our data is that carotenoids cannot be distinctive of a single leukemia subtype. At the most, our data suggest that carotenoids can be a possible biomarker of AML M5a when considering only the AML group. When comparing ALL B vs ALL T, or ALL B Ph+ vs ALL B Ph-vs ALL T, there are no clear differences from the morphological and qualitative evaluation of global clustering results.