// Lauren M. Rosati 1,* , Megan N. Kummerlowe 1,* , Justin Poling 2 , Amy Hacker-Prietz 1 , Amol K. Narang 1 , Eun J. Shin 3 , Dung T. Le 4 , Elliot K. Fishman 5 , Ralph H. Hruban 2 , Stephen C. Yang 6 , Matthew J. Weiss 6 and Joseph M. Herman 1,7 1 Department of Radiation Oncology & Molecular Radiation Sciences, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 2 Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 3 Department of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 4 Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 5 Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 6 Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 7 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors have contributed equally to this manuscript Correspondence to: Joseph M. Herman, email: // Keywords : pancreatic cancer, pancreatic ductal adenocarcinoma, metastatic, esophagus, esophageal metastasis Received : April 28, 2017 Accepted : May 20, 2017 Published : June 12, 2017 Abstract Purpose: We report a very unique case of an esophageal metastasis from a pancreatic ductal adenocarcinoma (PDAC) primary. Methods: After obtaining consent from the patient, all relevant records of the case were obtained and retrospectively reviewed. Results: At presentation, the patient was diagnosed with synchronous pancreatic and esophageal cancer. He received six months of neoadjuvant therapy including FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and stereotactic body radiation therapy (SBRT) to the pancreatic tumor followed by a combined pancreaticoduodenectomy and Ivor Lewis esophagectomy. Review of the final esophageal specimen revealed normal overlying squamous mucosa with an underlying focus of metastatic PDAC. The patient remains alive with no evidence of disease 17 months from surgery and 25 months from diagnosis. Conclusions: Differentiating an esophageal metastasis from a PDAC primary versus a synchronous esophageal carcinoma is very difficult despite state-of-the-art diagnostic techniques performed at a high-volume tertiary cancer center. Extensive evaluation and continued follow-up of PDAC patients presenting with a synchronous esophageal lesion in a multidisciplinary setting may help ensure efficient and accurate management. In our case, neoadjuvant FOLFIRINOX and SBRT to the primary PDAC tumor followed by surgery has been an effective approach for this patient.