Background: Cutaneous leishmaniasis is an infectious disease caused by the protozoa of Leishmania genus, which cause serious public health issues in endemic regions across 80 countries. The disease outcome is influenced by interaction between the parasite and immune system of its human host. Here, we report two cases of unusual and drug-resistant cutaneous leishmaniasis as an initial presentation of the underlying lymphoproliferative disorder.Case Report: Case 1 was a 43-year-old man with a history of cutaneous leishmaniasis presenting with an ulcerated and indurated plaque in proximity to the right eye along with ectropion, with multiple recurrences and resistance to multiple treatment plans. After multiple evaluations and hospitalizations, the patient was diagnosed with acute lymphoblastic leukemia (ALL). Case 2 was a 51-year-old man with a history of cutaneous leishmaniasis primarily presenting with an ulcerative papular lesion located on right forearm. The lesion was resistant to treatment, and two new ulcerated and indurated lesions appeared on the left ear and right zygoma with multiple recurrences and resistance to treatmen. During the course of treatment and further evaluations, chronic lymphocytic leukemia (CLL) was diagnosed.Conclusion: This case report presents ALL and CLL as possible underlying causes for resistance and recurrences in cutaneous leishmaniasis. Giving special attention to the patients’ signs and symptoms, as well as a thorough physical examination with proper paraclinical evaluations in patients with treatment failure, can be the key to identify underlying disorders.