Trichilemmal (pilar) cysts are common skin lesions that often present on the scalps of mature men and women. These cysts often become inflamed when the wall of the cyst ruptures, but few reports have addressed the immunologic features of this process.A 22-year-old female presented with rapidly growing nodule on her left cheek, with evidence of acute inflammation. Skin tissue for hematoxylin and eosin examination, as well as for immunohistochemical analysis was taken and reviewed. As controls, we utilized two archival, non-inflamed trichilemmal cysts. Hematoxylin and eosin staining demonstrated classic features of an inflamed trichilemmal cyst. No cytologic atypia was noted, and no significant number of mitotic figures was identified. Immunohistochemistry stains revealed that several cell cycle/tumor suppressor/apoptotic markers, antigen presenting cell markers, metalloproteinases and T cell response markers were highly expressed inside and around the disrupted cyst. The control, non-inflamed cysts were negative for the same markers. CD1a was also appreciated within the epidermis, suprajacent to the inflamed cyst.Upregulation and/or downregulation of selected cell cycle regulator and/or tumor suppressor/apoptotic markers, as well as antigen presenting cells and some protein kinases could recruit and activate T lymphocytes and other inflammatory cells to the non-disrupted cyst for unknown reasons. The immune response may be involved in the initial cyst rupture, or induced by an unknown alteration in the cyst. Larger studies are needed to address these questions.