Epstein-Barr virus (EBV) can cause frequently asymptomatic (or anicteric) and self-limited hepatitis, while occasionally may result in considerable cholestatic hepatitis. Herein, we describe the case of a previously healthy toddler (26 month old girl) with prolonged cholestasis, elevated serum transaminases, EBV serology compatible with recent EBV infection and positive anti liver kidney microsomal antibody type 1 which is characteristic of new-onset autoimmune hepatitis type 2. Liver biopsy was also typical of autoimmune hepatitis as attested by the presence of portal inflammation with predominant T-lymphocytes and plasma cells and interface hepatitis. Persistent EBV-related hepatitis was excluded by the absence of viral inclusions and steatosis on liver specimens and negative liver EBV-PCR. In conclusion, our case strongly suggests that in children with prolonged cholestatic hepatitis, positive EBV serology cannot exclude the presence of other causes of liver disease. In this context, autoimmune hepatitis should be considered as an alternate diagnosis, particularly when there is specific liver-related autoantibody detection. In such conditions, liver biopsy seems mandatory in an attempt to achieve a correct and timely diagnosis of a potentially catastrophic disease as autoimmune hepatitis. Although some cases of autoimmune hepatitis type 1 following EBV infection have been reported in adults, to the best of our knowledge, the present case of autoimmune hepatitis type 2 after EBV infection represents the first case in children ever reported in the English literature.