Mucins are complex mucosal glycoproteins that can be highly expressed by adenocarcinomas, having diagnostic, therapeutic, and biological significance. MUC13 encodes a cell surface membrane-anchored mucin expressed in the normal gastrointestinal tract, trachea, and kidney as well as colorectal, esophageal, gastric, pancreatic, and lung cancers. MUC13 protein expression was determined immunohistochemically in 99 sporadic colorectal cancers, assessing proportion of tumor cells stained, stain intensity, and localization. In normal colon, intense apical membrane and variable cytoplasmic MUC13 staining was present in both goblet and columnar cells, with strongest reactivity in the upper crypts and surface epithelium. All cancers showed staining of most tumor cells, being most conspicuous in the apical membranes of gland spaces. Left-sided tumors had a higher overall proportion of MUC13-positive tumor cells than right-sided tumors (P < .05), and high staining intensity was more frequent in adenocarcinomas (81%) than mucinous tumors (50%) (P < .05). Poorly differentiated and late-stage tumors were more likely to have high-intensity cytoplasmic staining (P < or = .025). Basolateral cell membranes were stained in 24% of cases, being more common in poorly differentiated tumors (55%) than well or moderately differentiated tumors (16%) (P < or = .001). Partial or full circumferential MUC13 staining was frequently observed in areas of tumor budding. Although MUC13 immunoreactivity was not predictive of patient outcome, there was a trend toward poorer outcome in patients with tumors showing basolateral MUC13. In summary, MUC13 was expressed abundantly by all colorectal cancers, with the highest expression in more poorly differentiated tumors.