Carbamoyl phosphate synthetase I (CPS1), normally found in hepatocytes and small-intestine (SI) enterocytes, is the antigen of Hep Par 1 antibody. Expression of CPS1 in invasive SI adenocarcinoma seems to be lost. We retrospectively collected 36 total specimens, which included 31 SI adenomas and 21 adenocarcinomas. We used 34 cases of duodenitis as a control group. Immunohistochemical and Western blot analyses were performed to determine CPS1 expression. The normal SI mucosa, all 34 cases of duodenitis, and all 29 adenomas with low-grade dysplasia demonstrated diffuse Hep Par 1 expression. Of the 21 invasive adenocarcinomas, 15 lost antigen expression (71%). These data are statistically significant (P < .05). Western blot analysis confirmed the immunohistochemical findings, with strong CPS1 expression within the normal mucosa and adenoma and complete loss in the invasive tumor. The differential expression of Hep Par 1 in dysplastic vs malignant tumors of the SI may be diagnostically useful in difficult cases.