© 2016, NATCO. All rights reserved. Malignancy following solid organ transplant remains a significant threat to the survival of cardiac transplant recipients. Plasma cell dyscrasias including multiple myeloma have been encountered in this population, and medication treatments traditionally used to treat these disorders demonstrate immunomodulatory effects that may have implications on the transplanted allograft. Lenalidomide is an immunomodulatory agent that has been used to treat plasma cell disorders, including light-chain amyloidosis (AL) and multiple myeloma, and represents such a class of medications in which the risks and benefits in the solid organ transplant population remain to be fully elucidated. This report highlights a clinical practice issue where the treatment of a patient's multiple myeloma with lenalidomide may have potentiated an episode of severe acute cellular rejection and further demonstrates the need for future investigation of the optimal treatment of plasma cell disorders including AL amyloidosis and multiple myeloma following solid organ transplantation.