Amyloidosis is a rare disorder that results in tissue deposition of insoluble fibrils. Systemic amyloid deposits are formed by immunoglobulin light chains or mutant protein, may involve various organs and cause organ damage. Heart involvement is observed in 50% of patients with light-chain amyloidosis and is a relevant factor for poor prognosis. A 68 year old white male with a significant past medical history received a 1/6 HLA matched orthotropic heart transplant for restrictive cardiomyopathy and diastolic congestive heart failure New York Heart Association class III. The native heart was found to be positive for amyloidosis (lambda light chain restricted). He had a prolonged and complicated post-transplant course during which he developed right ventricle failure, recurrent pleural effusions, adrenal insufficiency and end stage renal disease requiring hemodialysis. Multiple endomyocardial biopsies post-transplant were negative for rejection and amyloidosis. A bone marrow biopsy 2 months post-transplant was consistent with myeloma with no evidence of amyloidosis. He was treated with Cytoxan/ Bortezomib/ Dexamethasone x2 for 8 weeks with complete remission but continued to require hemodialysis 3 x weekly. Eight months later he received an autologous stem cell transplant with standard of care Melphalan 140 mg/mm2. His counts recovered on post-transplant day 12. He was discharged on post-transplant day 15 with a serum creatinine of 2.43 mg/dl which had decreased from a baseline of 2.97 mg/dl. His renal dialysis was discontinued, to be done on as needed basis and his urine output was 1700 cc on post-transplant day 21. He continues to be on prednisone and tacrolimus for his heart transplant. The case is interesting as the workup for amyloidosis pre-heart transplant was negative despite bone marrow, endomyocardial and abdominal fat pad biopsies. The diagnosis of multiple myeloma was made after his explanted heart showed amyloidosis. The generally accepted therapeutic approach to improve survival and quality of life is chemotherapy and autologous stem cell transplant. Bortezomib benefits elderly patients with newly diagnosed multiple myeloma. Identification of high risk patients with cardiac amyloidosis is a goal to implement individualized treatment strategies to enable curative therapy.