BACKGROUND: This article presents the first documented case of visceral leishmaniasis in an adult patient in Slovakia, with an unusual involvement of the colon. Leishmaniasis is a tropical parasitic infection transmitted by sandflies, predominantly occurring in developing countries. CASE PRESENTATION: The patient was a 57-year-old woman without comorbidities or immunocompromising conditions. The clinical presentation included non-specific symptoms such as prolonged fever, marked weakness, hepatosplenomegaly, and generalized lymphadenopathy. The diagnosis was established based on histopathological examination and bone marrow PCR, which confirmed the presence of Leishmania infantum amastigotes. After initiating treatment with amphotericin B, the patient's condition improved, but a relapse occurred shortly thereafter, presenting with colonic involvement-an extremely rare occurrence in immunocompetent patients. The diagnosis of relapse was confirmed by repeated histopathological examination and molecular analysis. Treatment was re-initiated with an extended regimen of amphotericin B and additional supportive therapy. CONCLUSION: This case highlights the importance of early diagnosis and targeted treatment of visceral leishmaniasis, even in non-endemic areas of the world. It emphasizes the need to consider this diagnosis in the differential diagnosis of patients with unexplained febrile conditions and hepatosplenomegaly, as the clinical presentation can often mimic various other infectious diseases or hematological malignancies, significantly complicating the diagnostic process.