We report the case of a 53-year-old male with recent travel to Guatemala and Belize who was diagnosed with cutaneous leishmaniasis (CL). He was treated empirically with miltefosine with no improvement and switched to amphotericin B upon species identification of , resulting in the resolution of his lesions. This case demonstrates that clinicians should recognize the importance of systemic therapy for treating complex CL, as well as the importance of identification of species type for tailoring treatments. Furthermore, while miltefosine has proven efficacious for CL in many New World locales, it has demonstrated lower cure rates for CL in Guatemala, and thus identification of the region of origin of the CL infection is imperative for further guiding treatment, which may vary according to the differences in drug potency or region-specific resistance rates.