Different types of association between leishmaniasis and cancer were established: leishmaniasis mimicking a malignant disorder, such as lymphoma; leishmaniasis arising as a difficult to diagnose and treat infection among patients receiving chemotherapy for various malignant disorders; simultaneous diagnosis of leishmaniasis and a neoplastic disorder in the same tissue samples of immunocom-promised patients; and direct involvement of Leishmania spp. in pathogenesis/occurrence of malignant lesions, especially of the skin and mucous membranes. Cutaneous leishmaniasis (CL) is a protozoan skin disease occurring in all the Middle East countries. Only the cutaneous form is a self-curing, which may develop a certain degree of immunity against the parasite, resulting in healing of the lesion(s). However, the parasites probably never disappear completely, since in situations where immune system is compromised, as in AIDS, or suppressed by cancer chemotherapy or in organ transplantation, Leishmania spp. may suddenly reappear. The cell-mediated immunity is responsible for skin lesion healing but humeral response plays a protective role against the disease. Skin biopsies from 65 parasitological proven cutaneous leishmaniasis patients from Egypt, Saudi Arabia, Jordan and Libya were histopathologically studied. The results showed that cutaneous leishmaniasis especially in hot areas pave the way to the mutation and development of skin cancer.