<p>Giant congenital melanocytic nevi (GCMN) are significant dermatological conditions requiring early interventions due to their large size and potential for malignant transformation. Current treatments predominantly involve surgical removal, which is not only time-consuming but also associated with substantial risks and complications. There is a critical need for alternative therapeutic approaches; however, progress has been hindered by a lack of suitable preclinical models that accurately reflect the heterogeneity of GCMN. To establish a GCMN patient-derived xenograft (PDX) model. We assessed the gross appearance and histological features of grafted nevi using two distinct approaches: cutaneous transplantation and subcutaneous implantation. We further determined an optimal graft thickness for survival and explored the mechanism underlying stable grafting. Nevi transplantation using the cutaneous method demonstrated a superior appearance, a more intact skin structure, and a higher melanocyte density compared to those in the subcutaneous method. Nevi with a thickness ≤ 1 mm demonstrated a high survival rate of 78.3% on murine dorsal skin. These surviving grafts closely resembled the original nevi in both morphological and histological characteristics, whose size remained virtually unchanged from one-month post-operation. Cases of regression appeared to closely correlate with insufficient microvascular networks. We successfully established a GCMN PDX model using a convenient cutaneous approach. This PDX model effectively recapitulated the morphological features and histological characteristics of patient nevi, providing a robust platform for evaluating the therapeutic effects and facilitating the development of innovative treatments for GCMN.</p>