Host immunosuppression is increasingly recognized as a significant risk factor for the development of a primary neoplasm. Chronic immunosuppressive therapy, as used in organ transplantation, may perturb the immunosurveillance ability of the host, making the patient more susceptible to virus-associated malignancies. We have taken care of a care of a child who received an orthotopic heart transplant and who then developed both a generalized lymphoproliferative disorder and a leiomyoma of the liver a year later. Epstein-Barr virus DNA was detected in a lymph node initially and the hepatic tumor cells subsequently. The former responded to a reduction in the immunosuppressive medications and the latter responded to surgical resection. This is the first report of a hepatic smooth cell neoplasm occurring following cardiac transplant and the development of two sequential Epstein-Barr virus-associated disorders in an immunosuppressed patient.