A 1-month-old child presented to our unit with jaundice and raised aminotransferases, γ-glutamyltranspeptidase and bilirubin. Metabolic diseases were ruled out and ultrasound found no alterations. Human herpesvirus type 6 (HHV-6) DNA was found in blood and saliva and IgG anti-HHV-6 in serum, and a diagnosis of HHV-6 hepatitis was made. In the following weeks, aminotransferase values remained raised while γ-glutamyltranspeptidase levels returned to normal in 45 days. At the age of 5 months symptoms and elevated aminotransferases persisted and immunohistochemistry performed on liver tissue allowed a diagnosis of progressive familiar intrahepatic cholestasis type 2 to be made. The patient is now 7 months old, and cholestatic jaundice and pruritus continue to be present.