Challenges in the differential diagnosis of desmoplastic melanomas include spindle cell squamous cell carcinoma, atypical fibroxanthoma, MPNST, and sarcoma, which were included in a study that reported 100% of desmoplastic melanomas as being SOX10-positive, while all histological mimics were SOX10-negative. The gene discussed is SOX10; the disease is sarcomatoid squamous cell carcinoma.