Systemic or localized lympho-adenomegaly is a common cause of access to the emergency department (ED), and differential diagnosis is often complicated. The combination of anamnesis, physical examination, laboratory tests, and instrumental diagnosis are extremely important to orientate toward a rapid and correct therapy, even if a prompt discrimination of the etiology of this lymphadenomegaly is not often possible. Our aim with this review is to improve the management of a differential diagnosis between hematological and infective diseases as leishmaniasis in ED and suggest quick diagnostic techniques that might be useful for early identification. Together in the review, we describe a case report of a young man affected from visceral leishmaniasis who presented to our ED and was incorrectly addressed to the wrong ward for the study of his condition. Subsequently, we focus on the clinical presentation of visceral leishmaniasis and compare it to the most common differential diagnoses that are usually taken into account in the management of such patients.