Aim: To determine if neoadjuvant chemoradiotherapy (nCRT) affects p53 and SOX2 expression in esophageal adenocarcinoma (EAC). Materials & methods: Comparison of p53 and SOX2 expression in 100 paired pre- and post-nCRT EAC samples. Results: Aberrant p53 was largely concordant (75/83, 90%), while 13/18 (72%) pre-nCRT samples with wild-type (WT) p53 staining, showed aberrant staining in paired post-nCRT samples. Similarly, 31/45 (69%) with previous WT SOX2 showed SOX2 loss in paired post-nCRT samples, whereas aberrant SOX2 loss was concordant in 50/55 (91%) cases. The prognostic values of both markers regarding survival differ before and after nCRT. Conclusion: Aberrant expression of p53 and SOX2 staining in EAC tissue is unaffected by nCRT. Conversely, the WT-staining pattern frequently changed to aberrant expression.