Plasmacytosis circumorificialis (PLC), a benign chronic inflammatory disease with an unknown pathogenesis, is characterized by erythema, erosion nodules and ulcers around the openings of the human body. In this report, we describe two cases of PLC successfully treated with topical tacrolimus. Interestingly, immunohistochemical staining revealed that prominent CD163(+) proinflammatory macrophages and IL-17-producing cells were infiltrating around plasma cells, which might suggest the reason for the therapeutic effect of topical tacrolimus on PLC.