We investigated whether microRNA-21 and microRNA-148a are predictive for neoadjuvant treatment in esophageal adenocarcinoma. Thirty-six patients with neoadjuvant therapy and surgical resection were included. FFPE tissue from biopsy and esophagectomy were analyzed using RT-qPCR. Results were correlated to histological tumor regression, histopathological variables, FDG-PET-CT and survival. MicroRNA-21 was significantly higher in esophagectomies than in corresponding biopsies (p = .027). No association of microRNA-21 or micro RNA-148a expression in tissue specimens with other clinical parameters was present. Although no influence of microRNA-21 and microRNA-148a on the response to neoadjuvant therapy was seen, upregulation of micro RNA-21 might represent an escape mechanism of tumor cells.