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The aim of this report is to present a case of a patient who developed unusual systemic hypersensitivity reaction to a red-pigmented tattoo and to discuss diagnostic difficulties in case of systemic reactions to tattoo ink. The patient reported erythroderma on his arms and chest accompanied by plaque elevation of red parts of his most recently performed forearm tattoo as his primary symptoms. His health condition entailed a prolonged topical and intravenous immunosuppressive therapy, which proved ineffective. Over a year after emergence of initial symptoms, he presented to the Plastic Surgery Clinic with generalized erythroderma, systemic lymphadenopathy, elevation and granuloma formation in red tattoos on his forearm and complaints of fatigue and inability to participate fully in work-related and social activities. The patient underwent six staged excisions with direct closures, flap plasties and full-thickness skin grafts. Following completion of each surgical resection, the patient’s symptoms gradually subsided. We find this case illustrative of a clinical challenge that delayed hypersensitivity reactions to red tattoos may pose. Furthermore, we provide insights on management of hypersensitivity reactions. This report underlines the importance of social awareness of and public health approach to tattoo complications as key to successful prevention, identification and treatment of adverse reactions to tattoos.