Canine leishmaniosis (CanL), caused by , is a major zoonotic disease primarily transmitted by sand flies. Unlike in adult dogs, the clinical course of CanL in puppies remains poorly characterized, regardless of the transmission pathway (i.e., vertical transmission or vector exposure). This study presents the first systematic literature review (SLR) focused on juvenile CanL, alongside an atypical clinical case report. A PRISMA-compliant search across four databases identified three eligible studies describing CanL in puppies (≤9 months, according to the current canine life stage guidelines). The case involves a 4.5-month-old puppy adopted from southern Italy with papulo-nodular skin lesions and generalized lymphadenomegaly as well as a mild normocytic normochromic anemia and increased C-reactive protein. infection was confirmed by serology, polymerase chain reaction (PCR), and cytology. The SLR suggests that dermatological lesions and/or lymphadenomegaly, whether associated with laboratory abnormalities, represent the most common clinical manifestations of CanL in puppies. In the presented case, the coexistence of systemic dissemination signs and papulo-nodular skin lesions, typically associated with vector-borne transmission, suggests the possibility of a dual route of infection by . Juvenile CanL should be considered in differential diagnoses and supported by thorough diagnostic evaluation and appropriate follow-up protocols.