Summary We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and presented characteristic transmission electron microscopic (TEM) findings of various‐sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular oedematous erythemas with small blisters lining the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils. Direct and indirect immunofluorescence tests revealed the presence of in vivo bound and circulating IgG autoantibodies to the keratinocyte cell surfaces. However, enzyme‐linked immunosorbent assays for desmoglein (Dsg) 1, Dsg3 and desmocollins 1–3 showed negative results. Immunoblotting using the full‐length human Dsg1 recombinant protein showed a positive band. TEM examination showed various‐sized vacuoles squashing the nuclei in many keratinocytes, resulting in rupture of the cells. Immunoelectron microscopic examination revealed IgG deposition over the entire keratinocyte cell surfaces, which spared the desmosomes. IgG antibodies were also present on the inside walls of the vacuoles around the nuclei of keratinocytes and on the cell surfaces of infiltrating eosinophils. This patient also had marked eosinophilia and high levels of thymus and activation‐regulated chemokine and interleukin‐5 in the serum. These results indicated a novel autoantigen on the nondesmosomal keratinocyte cell surfaces and the pathogenesis of bullous spongiotic change with inflammation in HP. What's already known about this topic? Herpetiform pemphigus (HP) is a rare variant of pemphigus characterized clinically by pruritic annular erythemas with vesicles resembling dermatitis herpetiformis and histopathologically by eosinophilic spongiosis without apparent acantholysis. The targets of IgG autoantibodies in patients with HP are usually desmoglein 1 and 3, which are both components of desmosomes. What does this study add? This study reports the unique case of a patient with HP with IgG autoantibodies reactive to nondesmosomal sites of keratinocytes and characteristic transmission electron microscopic findings of various‐sized vacuoles in keratinocytes, while desmosomal adhesion remained. Regarding pathogenesis, we speculate that the ballooning vacuoles might result in the bullous spongiotic changes without acantholysis seen in this patient. This study also focuses on the relationships between blood eosinophil counts, serum thymus and activation‐regulated chemokine levels and HP disease activity. Linked Comment: Yuan and Pan. Br J Dermatol 2019; 180:22.