An unusual case of syringosquamous metaplasia of the eccrine ducts caused by cytomegalovirus (CMV) is presented. The patient was HIV positive and had extensive excoriation of the perineum and vulva. Biopsy revealed the presence of herpes simplex virus (HSV) inclusions in the necrotic exudate, a CMV vasculitis and extensive involvement of the eccrine ducts. In addition to containing typical CMV inclusions, the eccrine ducts showed proliferation and squamous metaplasia. Inclusions of HSV were not seen within the eccrine ducts by light microscopy or immunohistochemistry. The extensive proliferation with accompanying squamous metaplasia superficially can resemble an infiltrating squamous carcinoma, but this was not evident to a great extent in this case. To the best of our knowledge, our case represents the first of syringosquamous metaplasia of eccrine ducts caused by CMV infection.