Background Kaposi's sarcoma (KS) is commonly thought to be derived from endothelial cells because of the predominant expression of endothelial markers in KS lesions. However, the heterogeneity of the spindle‐cell compartment makes the precise lineage relationship of KS tumour cells unclear. Cultured KS‐derived spindle cells constitutively overexpress antiapoptotic proteins and exhibit invasive properties, which suggests that they may adequately represent the tumour cells of KS. Objectives We aimed to investigate the expression of a wide variety of immunohistochemical markers by spindle cells derived from patch‐, plaque‐ and nodular‐stage lesions from patients with iatrogenic, sporadic and acquired immune deficiency syndrome‐related KS, and to review the data reported by other laboratories. Methods Cells from six KS cell cultures derived from four subjects were examined by immunostaining. Results Comparison of these data indicates that KS‐derived spindle cells generally express myofibroblast antigens but lack endothelial and/or leucocyte markers. Conclusions As the myofibroblast phenotype is not the predominant feature of KS tissues, our findings further substantiate the view that the in vivo dominant endothelial population represents a reactive hyperplasia rather than the true KS tumour process.