Mastocytosis, a disease that varies in its clinical presentation, is usually documented by histologic examination of lesional skin. However, no universally accepted histopathologic criteria exist for establishing the diagnosis of this disease. We have combined the method of morphometric point counting with the mast cell-specific stain, conjugated avidin, to accurately quantify mast cells in cutaneous tissue sections of mastocytosis. Using this histologic approach, we found that macules, papules, and nodules of mast cell disease had from ninefold to nearly a 160-fold greater mast cell content than was observed in normal skin and in several other cutaneous disorders. This technique also permitted the objective histologic stratification of mastocytosis skin lesions according to their mast cell density. Morphometric point counting in conjunction with conjugated avidin offers a simple and accurate method for establishing the diagnosis of mastocytosis.