Gallbladder cancer without serosal invasion is often diagnosed during the pathologic examination of a gallbladder removed for presumed benign disease. The role of reoperative procedures in these patients is not well established, making it important to define prognostic factors that predict cancer spread. To determine if the pattern of immunohistochemical staining with a monoclonal antibody against CA 19-9 could predict lymph node spread of cancer, 23 patients with gallbladder cancer without serosal invasion were reviewed. CA 19-9 reaction was present in pathology specimens from all 23 patients. Twelve samples (52.2%) showed CA 19-9 in the stroma adjacent to cancer cells, while the remaining 11 did not show any stromal staining against CA 19-9. Lymph node development was found in only 2 (18.2%) of these 11 patients in the nonstromal staining group and 9 (75%) of the 12 patients in the stromal staining group. As these differences were statistically significant, we conclude that immunohistochemical localization of CA 19-9 in gallbladder cancer may be useful in predicting the presence or absence of lymph node involvement, and in developing a rational approach for a reoperative procedure.