The histopathological evaluation of morphological features in breast tumours provides prognostic information to guide therapy. Adjunct molecular analyses provide further diagnostic, prognostic and predictive information. However, there is limited knowledge of the molecular basis of morphological phenotypes in invasive breast cancer. This study integrated genomic, transcriptomic and protein data to provide a comprehensive molecular profiling of morphological features in breast cancer. Fifteen pathologists assessed 850 invasive breast cancer cases from The Cancer Genome Atlas (TCGA). Morphological features were significantly associated with genomic alteration, DNA methylation subtype, PAM50 and microRNA subtypes, proliferation scores, gene expression and/or RPPA subtype. Marked nuclear pleomorphism, necrosis, inflammation and high mitotic count were associated with Basal-like subtype and have similar molecular basis. Omics-based signatures were constructed to predict morphological features. The association of morphology transcriptome signatures with overall survival in oestrogen receptor (ER)-positive and ER-negative breast cancer was first assessed using the METABRIC dataset; signatures that remained prognostic in the METABRIC multivariate analysis were further evaluated in five additional datasets. The transcriptomic signature of epithelial tubule formation was prognostic in ER-positive breast cancer. No signature was prognostic in ER-negative. This study provided new insights into the molecular basis of breast cancer morphological phenotypes. The integration of morphological with molecular data has potential to refine breast cancer classification, predict response to therapy, enhance our understanding of breast cancer biology and improve clinical management. This work is publicly accessible at www.dx.ai/tcga_breast