Whole‐genome sequencing of 17 tumour–normal pairs and whole‐exome sequencing in a further 71 tumour–normal pairs identified recurrent mutations in TP53, RB1, CDKN2A, PIK3CA, NOTCH1 and NFE2L2, as well as ADAM29 and FAM135B. The genomic landscape of oesophageal SCC was significantly different from that of oesophageal adenocarcinoma, highlighting the different therapeutic strategies that are needed in this disease. Here, ADAM29 is linked to neoplasm.