We describe a case of Mediterranean visceral leishmaniasis (VL) in a patient with pre-existing chronic hepatitis C, which caused high hepatitis C virus (HCV) plasma concentration and was followed by a rapidly growing hepatocellular carcinoma (HCC). The high HCV load was drastically and persistently reduced soon after treatment with liposomal amphotericin B suggesting a cause-effect interaction. Some data suggest that liposomal amphotericin B may have an immunomodulatory effect. VL may directly affect the liver function, but HCC has never been reported as a consequence of the disease. This case suggests that VL causes an increase in HCV replication, but, although the growth of the HCC can be defined as exceptional, a relationship with VL is not proven.