Cutaneous leishmaniasis is caused by infection with Leishmania spp. and presents with chronic ulcerations. Due to the diverse manifestations of leishmaniasis in immunosuppressed patients, it can mimic other diseases causing chronic wounds at different sites. This abstract presents two complex cases of cutaneous leishmaniasis in immunosuppressed patients, highlighting both diagnostic and therapeutic challenges and possible future trends. The first case involves a 42-year-old man with multiple sclerosis on immunosuppressive treatment who developed a progressive sacral ulcer that was initially misdiagnosed as chronic pilonidal disease. Histology and PCR later confirmed Leishmania infantum infection. Despite initial systemic treatment with liposomal amphotericin B, the lesion worsened, requiring a multimodal approach combining systemic miltefosine, intralesional meglumine antimonate and advanced wound care, which resulted in healing after almost one year. The second case is a 67-year-old man with insulin-dependent diabetes and severe psoriasis treated with methotrexate. He presented with a chronic ulcer on his thigh, initially thought to be a pressure ulcer due to diabetic polyneuropathy. Histology from a biopsy provided a crucial clue to a protozoan infection. Further diagnostic tests, including Leishmania IST-PCR and tissue culture, confirmed Leishmania infantum as the underlying cause of the infection. Treatment with liposomal amphotericin B and local paromomycin therapy resulted in significant improvement, although cure was delayed. Both cases highlight the need to consider cutaneous leishmaniasis in patients with a history of travel to endemic regions, particularly those receiving immunosuppressive therapies. Furthermore, with the increasing use of immunosuppressive biological agents for conditions such as autoimmune diseases, cancer and skin diseases, the number of cases of cutaneous leishmaniasis in immunosuppressed patients is expected to increase. This highlights the importance of a multidisciplinary approach combining systemic, local and wound management strategies for optimal outcomes.