Background <p>Understanding the shrinkage phenomenon after wide local excision of melanoma is critical for precise surgical planning and accurate histopathologic evaluation. However, the extent of shrinkage and its influencing factors are not fully established.</p> Methods <p>The present study is a retrospective analysis of 329 patients who underwent wide local excision for melanoma between 2018 and 2022 at our institution. Melanoma characteristics, anatomical location, patient age, and gender were collected to investigate correlations with specimen shrinkage from in vivo to ex vivo. Statistical analyses included ANOVA and various post-hoc tests to identify significant differences.</p> Results <p>Significant differences in specimen shrinkage percentages were found based on patient age and melanoma location. Younger patients exhibited greater shrinkage, likely due to higher skin elasticity. Additionally, certain body sites, such as the back, demonstrated higher rates of shrinkage compared to other areas.</p> Conclusions <p>These findings highlight that melanoma specimen shrinkage is influenced by both age and anatomical site, underscoring the importance of accounting for this phenomenon during surgical planning and in guidelines. Standardizing the definition of excision margins as in vivo measurements is essential to ensure adequate oncologic clearance.</p> <p><b>Level of Evidence:</b> Level III, risk/prognostic study</p>