Background: Histiocytoid Sweet syndrome is characterized by a predominant neutrophilicdermal infiltrate. Usual clinical differential diagnosis includes erythema multiforme, drugeruption, and erythema nodosum. Histiocytoid Sweet syndrome is considered anuncommon histopathological variant of the disease.Methods: We evaluated clinical, histopathological, and immunohistochemical findings of acase categorized as idiopathic histiocytoid Sweet syndrome in which clinical-epidemiological data raised the possibilities of Sweet syndrome, leprosy, and drug reaction.Results: Positive reaction to myeloperoxidase (MPO) in histiocytoid cells of the dermalinfiltrate, response to oral corticosteroids, clinical and laboratory investigation, and absenceof cutaneous lesions or clinical complaints within 1 year of follow-up are consistent with thediagnosis of idiopathic histiocytoid Sweet syndrome. CD68 (PG-M1) and CD15 positivecells were also present among dermal cells. Conclusions: Epidemiological data are relevant while considering a clinical differentialdiagnosis of Sweet syndrome that can be further expanded, from a histopathological pointof view, when dealing with the histiocytoid variant since neutrophils, macrophages, andimmature myelomonocytic cells with histiocytoid morphology are present. The significanceof the MPO positive mononuclear dermal cells are not completely established.