The evolutionary modifications of the clinical, histomorphologic, and immunopathologic features of both classic and immunodeficiency (ID)-associated Kaposi's sarcoma (KS) were investigated in relation to the immune status of the patients. The histologic picture was similar in the classic and ID-associated forms of the tumor. In classic KS, a variably dense reactive infiltrate was present, and its amount was inversely related to the age of the lesions; conversely, a scarce reactive infiltrate, with the absence of CD4+ cells, was always evidenced in ID-associated KS lesions, even when the immune status of the patient showed no abnormalities. This evidence supports the hypothesis that a specific impairment of skin-associated lymphoid tissue may be crucial to the development of ID-associated KS.