The paper presents a novel histochemical approach for evaluation of tryptase expression in the mast cell population. To study the selective effect of mast cells (MC) on the parameters of a specific tissue microenvironment, it is necessary to detail the molecular composition of their secretome and analyze the pathways of degranulation. The developed method for combined immunomorphological and histochemical tryptase staining protocols contributes to a more objective determination of the integral level of specific protease expression in the skin MC population. Extra visualization potentials of cytological features and specific aspects of tryptase processing expand efficiency of morphological analysis in both normal and pathological conditions.