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Aims and Background: The melanosome-associated proteins, also called HMB45 and melan-A, are also present in renal angiomyolipoma. The aim of the present study was to evaluate the expression of HMB45 and melan-A in mesenchymal cells of renal angiomyolipoma and to investigate their significance in the differential diagnosis., Methods: Twelve patients, 9 females and 3 males diagnosed with renal angiomyolipomas, were included in the present study. The most representative tumor tissue block was chosen from each case, and 5-microm sections were taken to poly-L-lysin-coated slides for immunohistochemical staining. The standard streptavidin-biotin immunoperoxidase method was used for immunostaining with HMB45 and melan-A antibodies., Results: All of the cases showed positive cytoplasmic immunostaining for HMB45 and melan-A. Melan-A expression was shown in smooth muscle component, adipose tissue and predominantly in the perivascular cells, whereas HMB45 immunoreactivity was stronger than melan-A expression in all cases., Conclusions: It was concluded that HMB45 and melan-A reactivity is a useful tool to distinguish renal angiomyolipomas from other primary and secondary mesenchymal and primary epithelial tumors. Melan-A and HMB45 share similar specificities for renal angiomyolipoma. In addition, such expression in renal angiomyolipomas may occur without any evidence of nevomelanocytic differentiation. Further research is required to determine the histogenesis of this entity.