Here we demonstrate that HNSCC cells with an endogenous PTPRD mutation are more sensitive to the JAK/STAT inhibitor JSI-124 than HNSCC cells harboring no PTPR family mutations, suggesting that HNSCC tumors with PTPRD mutations may be exquisitely sensitive to STAT3 inhibitors that are currently in preclinical and clinical development. The gene discussed is PTPRR; the disease is head and neck squamous cell carcinoma.