Although this immunoprofile is atypical due to the absence of HMB-45 and Melan-A, the retained S100 and SOX10 expression supports melanocytic differentiation. These markers are recognized as the most sensitive indicators of melanocytic lineage, particularly in spindle cell and desmoplastic variants of melanoma, where HMB-45 and Melan-A expression may be absent [13]. The tumor was negative for BRAF and NRAS mutations, findings that guided the decision to initiate immune checkpoint blockade as first-line therapy. The gene discussed is MLANA; the disease is melanoma.