The prognostic significance of histology has been well established in epithelial ovarian cancer (EOC). Clear cell and mucinous histologies are especially generally accepted to result in an adverse outcome because of their poor chemotherapy response. Previous reports suggested that class III beta-tubulin induced taxol resistance in association with a reduced effect on microtubule dynamic instability. Thus, this study aimed to evaluate class III beta-tubulin expression and examine whether the protein level of class III beta-tubulin was correlated with the histological difference in chemosensitivity. Class III beta-tubulin expression in EOC tissues (n = 80) was immunohistochemically scored into 4 groups (-, +/-, +, ++). High-level (+, ++) class III beta-tubulin expression was detected in 30 of 35 clear cell carcinomas, in 8 of 10 mucinous carcinomas, 5 of 11 endometrioid carcinomas, and 5 of 24 serous carcinomas. Nineteen patients were evaluable for response. In 5 responders, high-level class III beta-tubulin expression was not detected. On the other hand, it was detected in 10 of 14 nonresponders. In some ovarian cancer cell lines, we evaluated class III beta-tubulin expression by Western blot analysis. Class III beta-tubulin expression in nonserous carcinoma tended to be higher than that in serous carcinoma. Taxol-resistant SKOV cells showed high-level class III beta-tubulin expression compared with wild-type SKOV cells. Taxol sensitivity differing among histological subtypes in EOC is associated with the expression of class III beta-tubulin.