Loss of the tumor suppressor argininosuccinate synthetase 1 (ASS1) results in arginine auxotrophy, typical of chemoresistant, poor prognosis cancers, including hepatocellular carcinoma, melanoma, thoracic and urological cancers, and sarcomas.2, 3, 4, 5, 6, 7 Mechanistically, ASS1 loss promotes diversion of the arginine precursor, aspartate, for enhanced pyrimidine synthesis and tumor cell proliferation.8 The gene discussed is ASS1; the disease is melanoma.