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Mast cells are important in inflammatory processes and in the nonspecific immune response, and there are also indications that these cells are associated with the effectors of the specific immune response. Eosinophilic granular cells are frequently compared to mast cells, and some authors maintain that they are the same cells. In this study, we take a fresh look at the similarities and differences between these two cell types in Oncorhynchus mykiss . We evaluated the cytomorphology of each cell type with optical microscopy, their staining affinities, and their ultrastructure. We observed that mast cells were positive for CD117 (c-kit), while eosinophilic granular cells were negative for this marker. We propose that these two cell types have certain common characteristics but represent well-differentiated populations distributed in several Oncorhynchus mykiss tissues., Competing Interests: The authors declare that there are no conflicts of interest., (© 2021 The Authors.)