In this study, we aimed to analyze the effect of the 3D arrangement on the morphological features and expression of some peculiar key EMT markers in two different melanoma cells lines: A375 (BRAF V600E-mutant, the predominant BRAF mutation occurring in about 50% of cases), isolated from a primary melanoma, and BLM (NRAS-mutant, a mutation present in about 30% of patients), isolated from a lung metastasis. The gene discussed is NRAS; the disease is melanoma.