Objective: The aim of this report is to present the diagnostic and therapeutic approach in a case of non-specific orbital inflammation complicated with sight-threatening exposure keratopathy. Case presentation: An 81-year-old female patient presented to our Ophthalmology Department for left, painful, unilateral exophthalmia and decreased vision in the same eye. The clinical examination revealed left proptosis, inferior dystopia, upper lid edema, erythema and moderate retraction, ocular motility restriction, chemosis and corneal epithelial defect. The keratopathy complicated in evolution with hypopyon. The patient received treatment for the exposure keratopathy and, after every specific cause of unilateral exophthalmia was ruled out using imagistic and laboratory examinations, systemic corticosteroid treatment was initiated. Although the response to treatment was prompt, it was incomplete because of the long-standing evolution. Discussions: In this case, the diagnosis was difficult because a malignant breast tumor was encountered and an orbital biopsy was impossible to be performed. The presence of exposure keratopathy complicated with hypopyon imposed the exclusion of an infectious process and delayed the initiation of the corticosteroid therapy. Conclusions: The diagnosis and treatment of this disease represent a challenge given the need to rule out all the local and systemic conditions that may present with exophthalmia.