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Chronic hepatitis C virus infection is the leading etiology for liver transplantation in the United States. Recurrent hepatitis C occurs nearly universally in these patients and represents a serious posttransplantation complication. Despite the detailed characterization of the histologic features of both recurrent hepatitis C and acute cellular rejection (ACR) over the last decades, the pathologic distinction between these 2 conditions remains one of the greatest diagnostic challenges in liver pathology. An accurate diagnosis, nevertheless, plays an essential role in patient management, as different therapeutic strategies are used for these conditions. In this review, the clinicopathologic features of posttransplantation recurrent hepatitis C and ACR are discussed, with emphasis on distinguishing histopathologic features, morphologic variants, ancillary techniques, and diagnostic pitfalls.