We report a 35-year-old man who was referred to our dermatology department with multiple, nodular, ulcerated, and crusted lesions disseminated on the face, trunk, and extremities. He has a known diagnosis of Down syndrome. The past medical history also included vitiligo (for 20 years), hypothyroidism (for 2 years), and type-II diabetes mellitus (for 3 months). Direct smear of an ulcer was positive for leishmania. Skin biopsy confirmed the diagnosis. A leishmanin skin test was negative. Polymerase chain reaction (PCR) from two separate skin biopsies demonstrated the presence of Leishmania major. To our knowledge, this is the first report of disseminated cutaneous leishmaniasis (DCL) caused by L. major in Iran, and also the first report of association between DCL with Down syndrome, vitiligo, hypothyroidism, and diabetes mellitus.