Proposed scheme of the major steps of differentiation of MCs from uncommitted hematopoietic progenitors. Based on the current knowledge and on the data presented in this issue by Dahlin et al,¹  it can be postulated that CD34⁺/CD117⁺ BM uncommitted hematopoietic progenitors, which express neither CD13 nor FcεRI, can give rise to early committed circulating mixed MC/monocyte CD34⁺/CD117⁺ progenitors, which express CD13, but are still FcεRI⁻. Upon different culture conditions, these mixed progenitors can produce pure MC colonies, colonies containing only monocytes, or mixed MC/monocyte colonies. These CD13⁺ progenitors can further acquire the expression of FcεRI, as described by Dahlin et al. At this step, the progenitors are definitively committed to the MC lineage and may reach various tissues to acquire the corresponding mature phenotype, that is, a MC_T phenotype in mucosal tissues and a MC_TC phenotype in serosal tissues. Alternatively, also based on the present report, it can be postulated that CD34⁺/CD117⁺/CD13⁻/FcεRI⁻ BM uncommitted hematopoietic progenitors can reach the bloodstream and become directly FcεRI⁺, giving rise to another circulating MC-committed progenitor, which lacks the expression of the CD13 antigen, but might acquire it later. This latter progenitor might also reach the tissues where it differentiates terminally as described above. Red arrows represent pathways of differentiation where additional intermediary progenitors might exist, which have still not been described.