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Background: Mixed adenoneuroendocrine carcinomas (MANECs) are rare malignancies with both neuroendocrine and non-neuroendocrine components. To date, the prognosis of gastroenteropancreatic MANECs remains dismal, and treatment options are mainly based on guidelines for the treatment of pure neuroendocrine carcinomas or small cell lung cancer. Established first-line therapy in the metastatic situation is cisplatin and etoposide. Platinum derivatives are known to cause a variety of side effects also involving the visual system. Severe orbital and optic nerve toxicities have been described mainly after intracarotid infusion of cisplatin. Case Report: Herein we report a rare case of a 60-year-old male patient suffering from MANEC of the gastroesophageal junction with HER2/neu overexpression who developed severe orbital and ocular neurotoxicity (grade 3 according to CTCAE v4.03) after intravenous cisplatin. Conclusion: We discuss diagnostic approaches and differential diagnoses in this clinical situation. Before starting treatment with intravenous and topical steroids, it is crucial to rule out meningeal and cerebral spread as well as paraneoplastic and endocrine syndromes. [ABSTRACT FROM AUTHOR]