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We hereby report the course and management of a patient with human epidermal growth factor receptor 2 negative esophageal cancer who received neoadjuvant chemoradiation, surgical resection and subsequently palliative therapy for recurrent disease. The critical role of the staging procedure is discussed. Additionally the options of systemic palliative therapies are presented and the rationale for immuno-oncologic treatment is highlighted. The patient received pembrolizumab as second-line therapy, which unfortunately did not result in a response and caused minor autoimmune side effects.