Background The overexpression of estrogen receptor beta (ER beta) and its correlation with prognosis of malignant mesothelioma remains controversial and unexplored. This study aimed at studying ER beta expression in tumour tissue in patients with pleural mesothelioma and its association with clinical and pathological factors and survival analysis. Material and methods A prospective cohort study was conducted on patients who were diagnosed with malignant pleural mesothelioma (MPM) in Ain Shams university hospitals, the primary end point was to correlate ER beta overexpression that was analysed by immunohistochemistry (IHC) on paraffin tissue blocks with 1-year overall survival (OS) among MPM patients, the secondary endpoint was to correlate ER beta overexpression with 1-year progression free survival (PFS) and response to platinum-based chemotherapy among MPM patients. Results A total 42 MPM patients were included, High ER beta expression (modified Allred score 7-9) was reported in 9.5% of the patients (4 cases), moderate expression (modified Allred score 4-6) was reported in 28.6% of the patients(12 cases), weak and negative expression ( modified Allred score 0-3) was reported in 61% of the patients(26 cases), percent of ER beta positive cases was 69% of the total patients, there was no statistical difference as regard age (p value:0.8), sex(p value:0.4), stage (p value: 0.71), ECOG (p value :0.84) , histological subtype(p value:0.17) and response to platinum based treatment (p value:0.5) across the 3 groups of patients (high, moderate , weak and negative ER beta on tumour tissues) there was no statistically significant difference in OS and PFS for ER beta overexpression. Conclusion The overexpression of ER beta was not associated with improved OS or PFS in mesothelioma patients, despite high rate of ER beta positive cases in our analysis, larger sample size would be recommended for more solid conclusions