Background: Heat shock protein (HSP) 105 is a 105-kDa protein, recently discovered by serological analysis of recom-binant cDNA expression libraries prepared from tumour cells (SEREX), and is still undergoing intensive research. SEREX can define strongly immunogenic tumour antigens that elicit both cellular and humoral immunity. Previous studies have shown that HSP105 is a cancer testis antigen and is overexpressed in various internal malignancies. The expression of HSP105 has not been studied in skin cancers. Objectives: To assess the expression of HSP105 in skin cancers including extramammary Paget disease (EMPD), cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Methods: Samples of EMPD (n = 25), SCC (n = 23, of which three were metastatic lesions) and BCC (n = 23) were collected from patients treated in our department between January 2002 and December 2004. Western blot and immunohistochemical staining methods were used to investigate the expression of HSP105. Results: Results of Western blot analysis showed overexpression of HSP105 in EMPD and SCC, and minimal expression in BCC. Immunohistochemistry results showed that 56%of EMPD, 60%of primary and 100%of metastatic SCC highly expressed HSP105 while only 13%of BCC lesions showed increased staining. Conclusions: EMPD and SCC overexpress HSP105 while BCC does not. Tumours overexpressing HSP105 present ideal candidates for vaccination by HSP105-derived peptides or DNA. BACKGROUND: Heat shock protein (HSP) 105 is a 105-kDa protein, recently discovered by serological analysis of recombinase cDNA expression libraries prepared from tumor cells (SEREX), and is still undergoing intensive research. SEREX can define strongly immunogenic tumour antigens that elicit both cellular and humoral immunity. Previous studies have shown that HSP105 is a cancer testis antigen and is overexpressed in various internal malignancies. Objectives: To assess the expression of HSP105 in skin cancers including: extramammary Paget disease (EMPD), cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Methods: Samples of EMPD (n = 25), SCC (n = 23, of which three were metastatic lesions) and BCC n = 23) were collected from patients treated in our department between January 2002 and December 2004. Western blot and immunohistochemical staining methods were used to investigate the expression of HSP105. Results: Results of Western blot analysis showed overexpression of HSP105 in EMPD and SCC, and minimal expression in BCC. Immunohistochemistry results showed that 56% of EMPD, 60% of primary and 100% of metastatic SCC highly expressed HSP105 while only 13% of BCC Lesions showed increased staining. Conclusions: EMPD and SCC overexpress HSP105 while BCC does not. Tumors overexpressing HSP105 present ideal candidates for vaccination by HSP105-derived peptides or DNA.