Introduction: End-stage heart failure and advanced esophageal cancer carry an extremely poor prognosis with a disabling quality of life (QOL). Individually, the 3-year survival is poor; simultaneously, it is unreported, but predictably dismal. LVAD implantation as Destination Therapy (DT) for non-transplant candidates has proven to prolong survival with an improved QOL. However, some DT-LVAD patients have survived their cardiovascular condition only to discover that they have serious malignancies. Treatment of these cancers in an LVAD patient is challenging. Anecdotal reports are beginning to appear in the literature as the DTLVAD patient population continues to grow. Case description: A 72 year-old man with end-stage heart failure was implanted with a Heartmate II® LVAD as Destination Therapy. The surgery was uneventful and he was discharged on postoperative day 16. Seven months later, he developed melena and was found to have an ulcerated mass at the gastroesophageal (GE) junction that was pathologically adenocarcinoma. CT/PET scanning and upper endoscopic sonography staged the disease at III (T3N1M0). Subsequent imaging showed a lytic L4 lesion that was biopsy proven metastatic disease. Due to the presence of the LVAD, the patient was not a surgical candidate for resection. Treatment consisted of chemoradiation therapy in the following manner: Two cycles of Paclitaxel (Taxol®)-Carboplatin followed by Paclitaxel-Carboplatin with radiation therapy (XRT) to the GE junction for six weeks followed by maintenance Folinic Acid-Oxaliplatin-Fluorouracil (FOLFOX 6) every two weeks. Drug dosing was modified in accordance with complete blood count (CBC) results. Serial PET scans were performed to assess efficacy, showing a range of complete absence of abnormal 18F-FDG uptake to occasional uptakes in various locations with mild to moderately elevated maximal SUV units. At present, the patient is alive with a good QOL approximately 3.5 years from LVAD implantation and 3 years from esophageal cancer diagnosis. Results and Conclusions: Multi-disciplinary therapies were instituted to treat two lethal conditions: end-stage heart failure and advanced esophageal cancer. The combination of medical therapy with chemotherapy, interventional therapy with radiation, and surgical therapy with an LVAD proved efficacious in this otherwise fatal case. As more patients with end-stage heart failure are implanted with LVADs - particularly for DT - the likelihood of non-cardiac conditions will undoubtedly appear cancer among them. The challenge will be to determine how to best approach these conditions. This case illustrates the power of a collaborative approach in the management of this complex problem. Take home message: The use of the implantable LVAD has enabled patients with end-stage heart failure to live longer and with an improved QOL. As a result of not dying from heart failure, some patients will experience serious non-cardiac conditions including cancer. With the growing number of DT-LVAD patients worldwide, it will be imperative for healthcare providers to address the treatment of these maladies utilizing a multi-specialty approach.