INTRODUCTION: The pentavalent antimony (Sb 5) remains the drug of choice in the treatment of mucosal Leishmaniasis (LM), despite adverse effects. In the absence of response to therapy, amphotericin B is used, despite the low tolerance. The third option is pentamidine, known for the toxicity and risk of diabetes mellitus. OBJECTIVE: To report a patient with LM with multiple relapses after treatment with Sb 5 and amphotericin B responsive to pentamidine. CASE REPORT: Male, 50 years old, three years ago had rhinorrhea, nasal obstruction and dysphonia, infiltrative lesions in the nasal septum, palate, uvula and pillars, IDRM 15 mm, histopathology with chronic granulomatosis inflammation with the presence of amastigote and promastigotes isolated in culture. 5mgSb 5/Kg/day treatment was discontinued and abandoned in the fourth dose after laryngeal edema. Restarted treatment with improvement of the lesions, there was another drop in the thirty-dose. After six years, relapse occurred mucosa with good therapeutic response to doses of 47 5mgSb 5/Kg/day in an intermittent schedule. One year later, the second recurrence was treated with 3 g of amphotericin B. New recurrence after two years was treated with 80 doses of 5mgSb 5/kg/day, no significant improvement. Was started amphotericin B deoxycholate, interrupted with 50mg nephrotoxicity and was replaced by liposomal amphotericin B, also stopped by with 200mg nephrotoxicity. It was used pentamidine (4mg/kg) with improvement of symptoms and healing of the lesions. CONCLUSION: The administration of pentamidine was well tolerated and effective in a patient with LM with poor adhesion and resistance to Sb 5 and intolerance to amphotericin B.