Tumor heterogeneity has been shown for several cancers including breast cancer (BC). Despite the fact that expression of tumor markers may change throughout the metastatic process, rebiopsies at the time of recurrence are still not performed routinely at all institutions. The aims of the study were to evaluate changes in biomarker profiles during the metastatic process and to investigate whether previous anthracycline or endocrine therapy given in the adjuvant setting could affect the biomarker profile in metastatic lesions. We investigated the expression pattern of ER, HER2, TOP2a, TOP1, p53, Bcl-2, and Ki-67 in 110 paired samples of primary BC and corresponding asynchronous metastases. We found discordant expressions in primary tumor and metastasis for all biomarkers, although only significant for Ki-67. Changes in the expression profile of the metastatic lesions would have altered treatment decisions in 14% of patients. We found no effect of previous anthracycline or endocrine therapy on the expression profiles. Our data confirm that discordant expressions of biomarkers are common in BC and often carry therapeutic consequences. This emphasizes the need for biopsies from metastatic lesions, even in cases where the localization of the metastatic process is not easily accessible.