The primary gene panel for a syndrome with melanoma and colon cancer includes the melanoma genetic panel and genes that have at least a twofold increase in colon cancer risk including APC, BMPR1A, CDH1, EPCAM, GREM1, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53. Genes that have a strong clinical association also include AXIN2, CHEK2, POLD1, and POLE. The additional preliminary evidence (or research) panel could include ATM, BLM, BUB1B, ENG, FLCN, GALNT12, and MLH3 (Fig. 2). The gene discussed is SMAD4; the disease is malignant colon neoplasm.