There have been many reports indicating that the down-regulation of p21(WAF1/CIP1) is related to carcinogenesis and the development of various tumors; nevertheless, its association with epithelial ovarian cancer (EOC) remains controversial. In this study, we focused on serous ovarian cancer, which is the most prevalent histological type, and performed immunohistochemical analysis to examine the expression of p21(WAF1/CIP1) and p53 in 43 cases of serous-type EOC sourced from a single University Hospital: 14 stage I, 4 stage II, 21 stage III, and 4 stage IV. Positive p21(WAF1/CIP1) was found in 24 of 43 cases (56%), and positive p53 was detected in 21 of 43 cases (49%). Among stage III/IV cases, positive p21(WAF1/CIP1) staining was found in 11 of 25 cases (44%), and positive p53 staining was detected in 13 of 25 cases (52%). Univariate survival analysis for the entire cohort revealed that positive p21(WAF1/CIP1) was associated with a survival benefit. The 10-year survival rates of p21(WAF1/CIP1)-positive staining and p21(WAF1/CIP1)-negative staining were 82.4 and 39.5%, respectively, and there was a significant difference between the two groups (p<0.01). Overall survival for p21(WAF1/CIP1)-positive with p53-negative staining [p21(+)/p53(-)] was significantly different from p21(WAF1/CIP1)-positive with p53-positive [p21(+)/p53(+)], p21(WAF1/CIP1)-negative with p53-positive staining [p21(-)/p53(+)], and p21(WAF1/CIP1)-negative with p53-negative staining [p21(-)/p53(-)] (p<0.05). When only III/IV cases were evaluated, overall survival for [p21(+)/p53(-)] was significantly different from [p21(+)/p53(+)], [p21(-)/p53(+)], and [p21(-)/p53(-)] (p<0.05). These results suggested that the overexpression of p21(WAF1/CIP1) in conjunction with the loss of p53 expression was a stronger predictor of survival benefit than either molecule alone in Japanese serous-type advanced ovarian cancers with more than 10-year follow-up.