This is the first description in which the diagnosis of vanishing bile duct syndrome (VBDS) preceded the diagnosis of Hodgkin disease (HD) by several months, and for which patients received modifications to modern MOPP-ABV chemotherapy with successful clinical remission. VBDS is an uncommon form of liver disease manifested by severe cholestasis and progressive liver failure. We report 2 cases of stage IIIB pediatric HD and VBDS. Because VBDS is progressive and the only curative treatment is liver transplant, it is imperative to recognize that children with VBDS may also have concurrent HD.