Abstract:Melanoma is the most lethal form of skin cancer, and early detection is critical for improving patient outcomes. Although dermoscopy combined with deep learning has advanced automated skin-lesion analysis, progress is hindered by limited access to large, well-annotated datasets and by severe class imbalance, where melanoma images are substantially underrepresented. To address these challenges, we present the first systematic benchmarking study comparing four GAN architectures-DCGAN, StyleGAN2, and two StyleGAN3 variants (T/R)-for high-resolution melanoma-specific synthesis. We train and optimize all models on two expert-annotated benchmarks (ISIC 2018 and ISIC 2020) under unified preprocessing and hyperparameter exploration, with particular attention to R1 regularization tuning. Image quality is assessed through a multi-faceted protocol combining distribution-level metrics (FID), sample-level representativeness (FMD), qualitative dermoscopic inspection, downstream classification with a frozen EfficientNet-based melanoma detector, and independent evaluation by two board-certified dermatologists. StyleGAN2 achieves the best balance of quantitative performance and perceptual quality, attaining FID scores of 24.8 (ISIC 2018) and 7.96 (ISIC 2020) at gamma=0.8. The frozen classifier recognizes 83% of StyleGAN2-generated images as melanoma, while dermatologists distinguish synthetic from real images at only 66.5% accuracy (chance = 50%), with low inter-rater agreement (kappa = 0.17). In a controlled augmentation experiment, adding synthetic melanoma images to address class imbalance improved melanoma detection AUC from 0.925 to 0.945 on a held-out real-image test set. These findings demonstrate that StyleGAN2-generated melanoma images preserve diagnostically relevant features and can provide a measurable benefit for mitigating class imbalance in melanoma-focused machine learning pipelines.