A total of fifteen clinically and parasitologically proven adult cases of cutaneous leishmaniasis were studied for the demonstration of premalignant factor(s). The levels of antibodies against Leishmania parasite were measured with the indirect haemagglutination test (IHAT) and evaluated with the results of lymphoblast transformation test (LTT), a tumour suppressor gene (P53) and an asportic proteinase enzyme (Cathepsin D). Three patients (females) refused to be biopsied. The results showed a direct correlation between elevation of IHAT in 7/12 patients (Titers 1/128 to 1/512) and elevation of LTT in 7/12 patients (82 to 90%). On the other hand, two males with low (?) seropositive IHAT (1/64) and low LTT (20 & 40%) gave positive P53 antibody and moderate (1) and marked (1) degrees Cathepsin D. So, it is concluded that cutaneous leishmaniasis infection particularly chronic one favours the premalignant changes in the granulomatous lesions.