BACKGROUND: The term "leishmaniasis" defines a group of vector-borne diseases caused by species of the genus Leishmania and characterized by a spectrum of clinical manifestations. Parasite properties (infectivity, pathogenicity, virulence), host factors, and host responses regulate heterogeneous disease expression. Sicily is one of the major islands of the Mediterranean Basin and is considered to be a hypo-endemic area for cutaneous leishmaniasis. Leishmania infantum is the most common species on the island. METHODS: Fifty patients (both sexes and different ages) with lesions clinically suggestive of cutaneous leishmaniasis were recorded over a 1-year period. The diagnosis was based on positive slit-skin smear and histopathologic studies when needed. Polymerase chain reaction (PCR) was performed as test confirmation. RESULTS: Twenty-five patients had typical solitary lesions of cutaneous leishmaniasis. Multiple lesions were present in five patients. In 20 patients, the lesions were very unusual, including erysipeloid, zosteriform, and lupoid leishmaniasis. The results of Leishmania isoenzyme characterization identified Leishmania infantum as the species responsible for the 20 atypical cases. CONCLUSION: The global number of cases of cutaneous leishmaniasis in Sicily has increased in recent years, and such increases can be explained, in part, by the fact that, in this region, sandflies are present during a large part of the year. This is a result of the climatic variation in recent years (increasing temperature and humidity). There has also been an increase in the number of new and rare variants of cutaneous leishmaniasis. A knowledge of the unusual clinical variants of cutaneous leishmaniasis, as well as classical forms, allows early detection.