Plantar melanomas present unique diagnostic and surgical challenges owing to substantial regional variations in skin thickness. Although the Breslow thickness remains the primary criterion for staging and surgical excision, its application on plantar melanoma is complicated by the inherent thickness of the glabrous plantar epidermis, which may lead to tumor depth overestimation. Accurate assessment of plantar skin thickness is essential for optimizing staging accuracy and refining surgical margins. This study aimed to investigate plantar epidermal, dermal, and total skin thicknesses at 14 anatomical locations using high-frequency ultrasonography (HFUS) and histological analysis. A total of 35 ft (27 from cadavers and eight from patients) were examined. Mean total skin thickness was 1.71 +/- 0.31 mm, although mean epidermal thickness was 0.55 +/- 0.12 mm and mean dermal thickness was 1.16 +/- 0.27 mm. Significant regional variations were observed (p < 0.05), with the heel (S11) exhibiting the greatest thickness (2.19 +/- 0.29 mm) and the medial arch (S4) the least (1.41 +/- 0.26 mm). The results also included thickness ranking in order of the heel, forefoot, lateral arch, and medial arch. These findings suggest that plantar skin thickness correlates with mechanical stress distribution, with weight-bearing regions exhibiting greater epidermal and dermal thicknesses. By providing a comprehensive dataset of site-specific plantar skin thicknesses, this study enhances the precision of ultrasonographic melanoma assessment, refines tumor staging, and aids in optimizing excision margins. These findings offer clinically relevant anatomical reference points that may improve surgical decision-making, minimize unnecessary excisions, and enhance the prognosis of melanoma. Further studies should explore the correlation between ultrasonographic and histopathological measurements across diverse populations to strengthen their clinical applicability.