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This study investigates the differential expression of miRNA gene subtypes in tumoral versus benign nevi in individuals with melanoma, aiming to identify clinically significant correlations that could serve as reliable markers for assessing tumor stage and progression. Conducted between 2019 and 2022, this descriptive, quantitative observational research analyzed 90 formalin-fixed paraffin-embedded (FFPE) samples from the Pius Brinzeu County Emergency Clinical Hospital, Timisoara, including 45 samples of advanced-stage melanoma and 45 samples of pigmented nevi. miRNA purification and analysis were performed using the miRNeasy Kit and the Human Cancer PathwayFinder miScript miRNA PCR Array, with statistical analysis (including logistic regression) to determine associations with cancer staging, such as high Breslow index risk, number of mitoses, and vascular invasion. After the analysis and comparison of 180 miRNA gene subtypes, we selected 10 of the most upregulated and 10 most downregulated genes. The results revealed that hsa-miR-133b, hsa-miR-335-5p, hsa-miR-200a-3p, and hsa-miR-885-5p were significantly upregulated in melanoma samples, with fold changes ranging from 1.09 to 1.12. Conversely, hsa-miR-451a and hsa-miR-29b-3p showed notable downregulation in melanoma, with fold changes of 0.90 and 0.92, respectively. Additionally, logistic regression analysis identified hsa-miR-29b-3p (OR = 2.51) and hsa-miR-200a-3p (OR = 2.10) as significantly associated with an increased risk of a high Breslow index, while hsa-miR-127-3p and hsa-miR-451a were associated with a reduced risk. Conclusively, this study underscores the significant alterations in miRNA expression in melanoma compared to benign nevi and highlights the potential of specific miRNAs as biomarkers for melanoma progression. The identification of miRNAs with significant associations to melanoma characteristics suggests their utility in developing non-invasive, cost-effective diagnostic tools and in guiding therapeutic decisions, potentially improving patient outcomes in melanoma management. [ABSTRACT FROM AUTHOR]