Given the heterogeneous expression of HMB-45, p16, and PRAME in Spitzoid lesions, the diagnostic assessment of Spitz nevi in this study was primarily based on architectural and cytological criteria, supplemented by a limited immunohistochemical panel of melanocytic markers (including S100, SOX-10, and Melan-A/MART-1) available in a small-scale pathology laboratory. The gene discussed is PMEL; the disease is spitz nevus.