We report a 2-year-old girl with developmental delay who, from the age of 1 year, developed perniotic lesions of the hands and feet initially diagnosed as chilblain lupus. Histological examination showed features of epidermal necrosis with intraepidermal bulla formation, interface dermatitis, lymphocytic vasculitis with fibrinoid necrosis and thrombi formation, both superficial and deep dermal lymphocytic infiltrate, lymphocytic eccrine hidradenitis and absence of marked dermal edema. Subsequent investigations suggested a clinical diagnosis of Aicardi-Goutières syndrome (AGS), a rare genetic leukoencephalopathy. Recently, both AGS and familial chilblain lupus, an autosomal dominant form of systemic lupus erythematosus (SLE), have been shown to be allelic thus suggesting a common pathogenic basis. In addition, a phenotypic overlap is apparent between SLE and AGS. To our knowledge, this is the first comprehensive dermatopathological report of the cutaneous lesions seen in AGS, and our paper highlights the importance of considering AGS in the differential diagnosis of perniosis and chilblain lupus.