Although histological grade and muscular invasion are related to the malignant behaviors of endometrial endometrioid carcinoma, lymphatic and/or distant metastases are unexpectedly encountered, even in patients in the low-risk group. To re-evaluate additional reliable parameters to predict the risk of progression, we examined the immunohistochemical expression profiles of p53 and estrogen receptor (ER) β proteins. Patients with endometrial endometrioid carcinoma who underwent surgical treatment at our hospital (n = 154) were recruited to this study, and the significance of the relationships between the incidence of regional lymph node metastasis and/or postoperative recurrence and clinical or experimental parameters was evaluated. By multivariate analysis, we found that histological grades, detection of immunoreactive p53 (positive rates more than 10%, p53-stained), and high expression of ERβ (high-ERβ) were independently associated with metastasis and/or recurrence. Among these parameters, the sensitivity and negative predictive values of high-ERβ were very high (up to 100%). In the population with high-ERβ, the positive rates of metastasis and/or recurrence were 61.1% in the p53-stained group and 21.9% in the p53-non-stained (negative) group. Furthermore, the positive rate in the group showing myometrial invasion of more than 1/2 and showing both p53-stained and high-ERβ was 80%. The disease-free survival of patients who were double-positive for p53-stained and high-ERβ was significantly shorter than that in other patients. In summary, our findings showed that increases in ERβ and p53 immunoreactivity were significantly correlated with the incidence of metastasis and/or recurrence in endometrial endometrioid carcinoma, suggesting that double-positivity for p53-stained and high-ERβ may provide a promising clinical indicator to predict the risk of progression.