Ets-1 transcription factor has been associated with tumor progression in various carcinomas, but its expression in malignant melanoma was only recently described. The study was conducted in two steps: exploratory and confirmatory. In the first step, we studied 69 primary melanomas, 28 metastatic melanomas, 10 usual intradermal nevi and 13 various melanocytic skin lesions. In the second step, an additional group of 98 patients with follow-up of up to 200 months was also evaluated. Immunohistochemical analysis of formalinfixed/paraffin-embedded tissues was performed using 1G11 antibody and polymer conjugate for visualization. While Ets-1 was variably expressed in 83% primary melanomas in exploratory and 69% in the confirmatory group, the expression of Ets-1 was also found in normal benign melanocytes and all nevi. Analysis of the exploratory group revealed lower expression of Ets-1 in primary melanomas than in common nevi (P ¼ 0.048, Mann-Whitney U-test) and metastatic melanomas expressed significantly less Ets-1 than primary melanomas (P ¼ 0.015, Mann-Whitney U-test). There was a negative correlation between Ets-1 expression and the largest dimension of the primary tumors (r ¼ 0.23, P ¼ 0.034, Spearman's correlation rank test), but no correlation with the depth of tumor invasion (Breslow thickness) or the presence of ulceration was found. Analyses of the confirmatory group revealed no association between Ets-1 expression with disease-specific survival or time to treatment failure. However, a statistical trend was found for worse outcome for those primary melanomas that had strong expression (H-score 4100) of Ets-1 (P ¼ 0.054). Ets-1 is expressed in benign melanocytes probably due to their neural crest origin. We conclude that Ets-1 expression cannot be used to differentiate between benign and malignant melanocytic lesions and it has no definite association with clinical outcome. At the same time, its role in tumor progression in some cases of malignant melanoma cannot be entirely excluded. Keywords: Ets-1; malignant melanoma; survival; neural crest Malignant melanoma originates from melanocytes derived from the neural crest. 1 It is the most deadly form of skin cancer, whose incidence is rapidly increasing worldwide. 2 To date the most reliable prognostic marker of malignant melanoma is the vertical thickness (Breslow thickness) of the primary tumor. 3,4 Although progression of malignant melanoma occurs through a series of well-defined steps, the knowledge of genetic and phenotypic background for the disease is still rather scarce. The proto-oncogene ETS-1 belongs to the ETS family of transcription factors that also include, among others, ets-2, elf-1, fli-1 and PU-1. 5-7 Ets-1 plays an important role in cancer progression due to its ability to activate transcription of metastasis-, angiogenesis-and invasion-associated genes. [8][9][10][11][12] In a limited study on 10 melanomas and 24 benign melanocytic lesions, Keehn et al 13 recently reported expression of the Ets-1 in melanocytic lesions and suggested that E...