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The marked increase in the incidence of melanoma coupled with the rapid drop in the survival rate after metastasis has promoted the investigation into improved diagnostic methods for melanoma. High-frequency ultrasound (US), optical coherence tomography (OCT), and photoacoustic imaging (PAI) are three potential modalities that can assist a dermatologist by providing extra information beyond dermoscopic features. In this study, we imaged a swine model with spontaneous melanoma using these modalities and compared the images with images of nearby healthy skin. Histology images were used for validation.