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Background: Overexpression of estrogen receptors in malignant pleural mesothelioma has shown to be a good prognostic marker of survival and the use of selective estrogen receptor beta agonists (ERb) increases the susceptibility to antitumor treatment. Method: Longitudinal,retrospectiveand unicentric study that analyzes the response of malignant pleural mesothelioma with an expression of ERb to chemotherapy in the first line. The study had 22 patients pathologically diagnosed with malignant pleural mesothelioma between April 2014 to September 2015 at the National Institute of Respiratory Diseases, who underwent immunohistochemistry for ERb (mouse monoclonal antibody PPG5/10), used a qualitative system determined by direct observation of the pathologist with a scale 1+ for weak staining and 3+ for very intense staining, as well as the percentage of expression, was considered as high when it was increased to 50% of the cells. The primary endpoint was overall survival and ERb expression variable; secondary outcomes were progression-free survival and response rate to chemotherapy based on RECIST 1.1. Result: The sample is formed by 13 men (59.1%) and 9 women (40.9%), with a clinical stage of IV in 54.5%, III in 36.4%, II and IA both with 4.5%. Were smokers 54.5% with an average of 5.9 packs/year. In 95.5% there was an epithelioid pattern and 3.5% was biphasic. The 77.2% of the patients expressed a high percentage ERband 22.8% a low or null percentage. The response to the treatment by RECIST 1.1 was 54.5% for partial response (12 patients), stable disease in 22.7% (5 patients) and progression 13.6% (3 patients), no patient had a complete response. Of the patients who had a partial response, 75% (9 patients) had a high percentage of ERb expression in the tumor cells and 25% had a low or null percentage. The progression-free survival of patients with high ERbexpression had a median of 12.2 months compared to 9.3 months with low or null expression (p ¼ 0.67, 95% CI 4.5 -12-9), overall survival was 19.5 months in those with high expression of the receptor and 10.3 months for patients with low or null expression (this had a greater tendency to be higher in the ERb high expression for 9.2 months) (p ¼ 0.054, 95% CI 9.79-10.01) Conclusion: ERb high expression in patients with an advanced clinical stage of malignant pleural mesothelioma was associated with a better response to chemotherapy treatment (without being statistically significant), with a better progression-free survival and possibly overall survival trend.