A 2 yr old female intact flat-coated retriever dog was presented for evaluation of a histologically diagnosed cutaneous Langerhans cell histiocytosis of the muzzle with right mandibular nodal metastasis and suspected prescapular lymph node metastasis. Chemotherapy (lomustine 60 mg/m2 by mouth as a single dose) and glucocorticoid therapy (prednisone ∼20 mg/m2 by mouth every 24 hr) were initiated. Progressive disease occurred 21 days after lomustine administration. Doxorubicin (at 30 mg/m2 IV every 3 wk) was administered as a second-line therapy. Prednisone was continued at the same dose. Partial response was noted 1 wk after initiation of doxorubicin and sustained through doxorubicin #2. Complete remission was achieved following doxorubicin #3 (63 days from the start of doxorubicin rescue therapy). Progressive disease was noted after doxorubicin #5, for a total duration of response to doxorubicin of 105 days. Further rescue treatment with vinorelbine at 15 mg/m2 IV was elected. Progressive disease and clinical decline were noted 1 wk after initiation of vinorelbine. The patient was euthanized because of clinical decline 126 days after histopathologic diagnosis and 114 days after chemotherapy treatment was initiated.