Immunoreactive lysozyme was readily detectable in canine histiocytic disorders including systemic histiocytosis, malignant histiocytosis and granulomatous panniculitis. Lysozyme was less reliable as a histiocytic marker in cutaneous histiocytoma; forty percent of these tumors were negative for lysozyme expression. The marked heterogeneity in lysozyme expression in cutaneous histiocytoma may indicate that a proportion of these tumors show relatively primitive histiocytic differentiation and do not express lysozyme. Alternatively, this same proportion may exhibit a phenotype akin to cutaneous Langerhans cells which do not contain lysozyme. Lysozyme was not detectable in the tumor cells in lymphomatoid granulomatosis, atypical cutaneous histiocytoma, and histiocytic lymphosarcoma. Other evidence that these three disorders do not represent true histiocytic proliferative disorders is discussed.