Kaposi's sarcoma (KS) is a complex, multicellular growth, the pathogenesis of which remains unclear. Endemic African Kaposi's Sarcoma (KS) is characterized by its epidemiological peculiarities, protean clinical manifestations and an unpredictable natural history. A wide spectrum of clinical manifestations occurs, although the reasons for the heterogeneity remain unclear. Clinical observations in the presentation of human immunodeficiency virus (HIV)-associated epidemic African KS show a considerable overlap with endemic African KS obscuring the conventional binomial concept of African KS which was developed in light of the HIV epidemic. It is probable that once the KS lesions are expressed clinically, the subsequent spectrum and behaviour of all forms of African KS are consequential upon a complex interplay between the nature of the host cell-mediated immune responses and the putative aetiological factor(s).