Mucinous adenocarcinoma is an uncommon subtype of colorectal cancer (10–20%), defined by extracellular mucin comprising more than half of the tumor and is associated with increased lymphatic involvement in early stages. Endoscopically, mucin may appear as “droplet-like” material, a nonspecific but important finding during endoscopic submucosal dissection (ESD). We present two cases in which mucin droplets were visualized in the resection plane, with different distribution and histology. In the first case, a recurrent 30-mm rectal lesion contained mucin infiltrating deeper layers, and histology confirmed mucinous adenocarcinoma. In the second case, a 30-mm colonic lesion showed mucin confined to the submucosa; en bloc resection revealed high-grade dysplasia with mucin-draining glands. Mucin during ESD may indicate malignancy, although it can also occur in benign lesions.