Gastrointestinal cancers, including esophageal, gastric, liver, pancreatic, and colon, shed subcellular components into the blood stream and/or intestinal lumen. These targets include circulating tumor DNAs (ctDNAs), circulating microRNAs (miRNAs), circulating tumor cells (CTCs), and exosome encapsulated DNA/miRNAs. These targets can be detected in biofluids, such as blood, urine, saliva and feces. Several morphologies of nucleotides are found in biofluids: free floating DNA/miRNA, argonaute 2 (Ago2)/high-density lipoprotein (HDL) associated miRNA, and exosome encapsulated DNA/miRNA, which are secreted from cancer cells in diverse patterns. Apoptotic or necrotic cells directly shed components extracellularly (passive secretion) as ctDNAs, while living aggressive cancer cells secrete encapsulated protein-associated miRNAs in exosomes (active secretion).