For the first time, we revealed the intratumour heterogeneity within ER+ breast cancer by the application of ST and scRNA‐seq analyses on three unique models, including two ‘ER‐high’ PDXs (GS3 and SC31) with opposite responses to oestrogen, followed by validation through an oestrogen‐accelerating ‘ER‐low’ PDX (GS1). Here, ESR1 is linked to breast carcinoma.