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Polymethyl-methacrylate (PMMA) as part of bone cement is a widely used material in the context of orthopaedic implants and also in cranioplasty. Although PMMA is characterised by excellent biocompatibility with low intrinsic toxicity and inflammatory activation, a minor portion of patients develop allergic reactions. We present the case of a 39-year-old woman with an increasing headache and a corresponding erythema over the parieto-occipital cranioplasty, which was performed 42 days prior using a PMMA compound. A patch test specific for bone cement components confirmed the diagnosis of a PMMA delayed-type hypersensitivity reaction. The prevalence of allergic reactions to bone cement components are known to vary from between 0.6% and 1.6%, however no adequate, pre-interventional diagnostic tool is currently available. Therefore, physicians are required to consider this differential diagnosis even after an extremely delayed onset of symptoms. This case describes the first ever-reported case in the literature of hypersensitivity to bone cement cranioplasty.