As many other physicians and researchers, we have had the great pleasure to be fellows in the laboratory of Dean Metcalfe, the Laboratory of Allergic Diseases, National Institute of Allergic and Infectious Diseases (NIAID), NIH, Bethesda, USA (Figure [1](#fig-cap-0001)). The open atmosphere, research driven by curiosity, hypotheses originating from clinical observations, and mutual trust and respect are the cornerstones of Dean’s mentorship. Dean and his laboratory have made major contributions on mast cell biology, from basic studies on the regulation of mast cell development and functions, to clinical studies on mast cells in diseases, such as systemic mastocytosis. After more than 50 years of exploring human mast cells, Dean’s impact on what we know today about these cells, their biology and how they affect diseases is outstanding and unique.