The p120ctn protein (formerly p120CAS) is an armadillo family member that associates directly with the cytoplasmic tail of E-cadherin and participates in the junctional complex responsible for cell-cell adhesion. Since reduced cell-cell adhesion is associated with metastasis in colorectal cancer and other neoplasms, we hypothesize that reduced expression of p120ctn may be related to metastasis in colorectal tumors. Here we describe a study of p120ctn expression in 44 primary human colorectal adenocarcinomas. As detected by immunohistochemical methods, we find altered p120ctn staining patterns in 86% of the cases. Regional complete loss of expression is seen in 18% of the cases, and it correlates with high stage disease and nodal metastasis as well as decreased survival. Although this is a preliminary study, it suggests that downregulation of p120ctn in colon cancer may be associated with metastasis and poor clinical outcome.