Histiocytic diseases include cutaneous reactive histiocytosis (CRH), systemic reactive histiocytosis, cutaneous histiocytoma, histiocytic sarcoma and malignant histiocytosis. CRH lesions are consistent with a reactive inflammatory process in response to persistent antigen and its clinical course and response to therapy suggest an immunoregulatory dysfunction. Lesions consist of multiple, nonpruritic and nonpainful cutaneous nodules and plaques predominantly on the head, neck, perineum, scrotum, and extremities. Histopathologically there is a diffuse "bottom-heavy" angiocentric infiltrate composed of histiocytes, lymphocytes, and neutrophils which tracks along adnexa to the superficial dermis. In more advanced lesions the pattern is diffuse. In the case reported herein a three-years old mixed-breed female dog was presented with multiple cutaneous non alopecic or partially alopecic, erythematous, nonpruritic and nonpainful nodules and plaques, measuring 1-4 cm in diameter, localized on the planum nasale, eyelids, face, dorsal thoracic region and forelimbs. Histopathology revealed an intense angiocentric, periadnexal to diffuse infiltrate of predominantly histiocytes, lymphocytes and neutrophils in the dermis, more intense on the deeper areas of the lesion. Occasionally the infiltrate had a pyogranulomatous appearance. Fite-Faraco stain revealed acid-fast bacilli within macrophages, more frequent on the deep parts of the infiltrate. A diagnosis of cutaneous mycobacteriosis was made and the patient was treated with doxycycline for two months. Since no clinical response was attained, a diagnosis of CRH was considered and the therapeutic protocol was changed to prednisone and azathioprine, both 2 mg/kg s.i.d., and the lesions disappeared after three weeks. The patient was kept under azathioprine (1 mg/kg s.i.d.) and remains asymptomatic. CRH has been considered an idiopathic or sterile dermatopathy. But with the use of PCR, a correlation to cutaneous mycobacteriosis and leishmaniosis has been made. In the present case, mycobacteria apparently triggered the histiocytic reaction and the unresponsiveness to the antibiotic probably was due to the persistence of the inciting antigens even after the bacteria were eventually killed. There are only a few reports on the responsiveness of CRH to therapy. In some cases high doses of glucocorticoids were necessary to suppress the clinical signs or prevent recurrence. However, in our opinion identification and control of the etiological agent, i.e., the antigen, may be essential to prevent recurrence.