Background/Aims: We examined the expression of p53, K-ras, and Ki-67 in extrahepatic bile duct (EHBD) carcinoma, dysplasia, hyperplasia, and normal tissues. Then, their clinical significance was determined. We also investigated if dysplasia and hyperplasia are the precancerous lesion in EHBD carcinoma. Methods: Specimens of 23 patients with surgically resected EHBD carcinoma were classified into normal, hyperplasia, dysplasia, and carcinoma. Then, they were immunostained to examine the expression of p53, K-ras, and Ki-67 antibody. Results: p53 was detected in 46.7% of dysplasia and 66.7% of carcinoma but not in hyperplasia. K-ras was positive in 46.7% of dysplasia and 55.6% of carcinoma but not in hyperplasia. Ki-67 was positive in 18.1% of hyperplasia, 73.3% of dysplasia, and all the carcinoma. None of them was detected in normal tissue. There was no significant correlation between p53 immunoreactivity and gender, histological grade, stage of EHBD carcinoma, and survival. K-ras and Ki-67 immunoreactivity was not associated with gender, age, histological grade, stage of EHBD carcinoma, and survival. Conclusions: These data suggest that p53 and K-ras mutations may have a role in the carcinogenesis of EHBD carcinoma and that dysplasia may be a precancerous lesion of EHBD carcinoma. Ki-67 may be useful in differentiation of carcinoma from dysplasia. There is no prognostic relationship significantly between p53, K-ras, Ki-67 expression, and the clinicopathologic parameters. (Korean J Gastroenterol 2001;38: 112-119)