BackgroundThere are few prospective studies on the correlations between MRI features and whole RNA-sequencing data in breast cancer according to molecular subtypes. The purpose of our study was to explore the association between genetic profiles and MRI phenotypes of breast cancer and to identify imaging markers that influences the prognosis and treatment according to subtypes.MethodsFrom June 2017 to August 2018, MRIs of 95 women with invasive breast cancer were prospectively analyzed, using the breast imaging-reporting and data system and texture analysis. Whole RNA obtained from surgical specimens was analyzed using next-generation sequencing. The association between MRI features and gene expression profiles was analyzed in the entire tumor and subtypes. Gene networks, enriched functions, and canonical pathways were analyzed using Ingenuity Pathway Analysis. ThePvalue for differential expression was obtained using a parametricFtest comparing nested linear models and adjusted for multiple testing by reportingQvalue.ResultsIn 95 participants (mean age, 53 years ± 11 [standard deviation]), mass lesion type was associated with upregulation ofCCL3L1(sevenfold) and irregular mass shape was associated with downregulation of MIR421 (sixfold). In estrogen receptor-positive cancer with mass lesion type,CCL3L1(21-fold), SNHG12 (11-fold), and MIR206 (sevenfold) were upregulated, and MIR597 (265-fold), MIR126 (12-fold), andSOX17(fivefold) were downregulated. In triple-negative breast cancer with increased standard deviation of texture analysis on precontrast T1-weighted imaging,CLEC3A(23-fold),SRGN(13-fold),HSPG2(sevenfold),KMT2D(fivefold), andVMP1(fivefold) were upregulated, andIGLC2(73-fold) andPRDX4(sevenfold) were downregulated (all,P< 0.05 andQ< 0.1). Gene network and functional analysis showed that mass type estrogen receptor-positive cancers were associated with cell growth, anti-estrogen resistance, and poor survival.ConclusionMRI characteristics are associated with the different expressions of genes related to metastasis, anti-drug resistance, and prognosis, depending on the molecular subtypes of breast cancer.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13058-023-01668-7.