The article discusses the mechanisms of melanoma progression and treatment resistance, focusing on the role of cancer stem-like cells (CSCs). Melanoma is a heterogeneous tumor composed of genetically divergent subpopulations, including a small fraction of CSCs and many non-CSCs. CSCs are characterized by unique surface proteins and aberrant signaling pathways that contribute to melanoma progression, drug resistance, and recurrence. Key genetic alterations in melanoma include mutations in BRAF and NRAS, with BRAF V600E being the most common. Despite targeting BRAF V600E improving survival, long-term efficacy is limited due to acquired resistance. Drug resistance develops through mechanisms involving reactivation of MAPK signaling pathways. CSCs play a critical role in melanoma progression, drug resistance, and recurrence. Melanoma heterogeneity is driven by genetic, epigenetic, and phenotypic factors, including mutations in genes like MITF, CDKN2A, and PIK3CA. Epigenetic changes, such as DNA methylation, also contribute to melanoma progression and resistance. CSCs exhibit plasticity, allowing them to switch between CSC and non-CSC states, which contributes to drug resistance. Mechanisms of resistance include the activation of alternative signaling pathways, such as PI3K/AKT and MAPK, and the development of compensatory mechanisms. CSCs are resistant to chemotherapy and radiation due to their ability to repair DNA and express ABC transporters. Immune evasion strategies, including the secretion of immunosuppressive factors, also contribute to melanoma progression. Targeting CSCs and understanding their mechanisms is crucial for developing effective therapies for melanoma.The article discusses the mechanisms of melanoma progression and treatment resistance, focusing on the role of cancer stem-like cells (CSCs). Melanoma is a heterogeneous tumor composed of genetically divergent subpopulations, including a small fraction of CSCs and many non-CSCs. CSCs are characterized by unique surface proteins and aberrant signaling pathways that contribute to melanoma progression, drug resistance, and recurrence. Key genetic alterations in melanoma include mutations in BRAF and NRAS, with BRAF V600E being the most common. Despite targeting BRAF V600E improving survival, long-term efficacy is limited due to acquired resistance. Drug resistance develops through mechanisms involving reactivation of MAPK signaling pathways. CSCs play a critical role in melanoma progression, drug resistance, and recurrence. Melanoma heterogeneity is driven by genetic, epigenetic, and phenotypic factors, including mutations in genes like MITF, CDKN2A, and PIK3CA. Epigenetic changes, such as DNA methylation, also contribute to melanoma progression and resistance. CSCs exhibit plasticity, allowing them to switch between CSC and non-CSC states, which contributes to drug resistance. Mechanisms of resistance include the activation of alternative signaling pathways, such as PI3K/AKT and MAPK, and the development of compensatory mechanisms. CSCs are resistant to chemotherapy and radiation due to their ability to repair DNA and express ABC transporters. Immune evasion strategies, including the secretion of immunosuppressive factors, also contribute to melanoma progression. Targeting CSCs and understanding their mechanisms is crucial for developing effective therapies for melanoma.