Deletions or mutations of Smad4 (also known as DPC4, deleted in pancreatic cancer), a tumor suppressor [13] and the only known co-Smad protein in TGF-β-, activin- and bone morphogenetic protein-signaling, are found in various epithelial tumors, including pancreatic carcinoma [14,15], esophageal carcinoma [16], colorectal carcinoma [17], renal cell carcinoma [18], as well as breast carcinoma [19,20]. The gene discussed is SMAD4; the disease is hereditary clear cell renal cell carcinoma.