The BRMS1 metastasis suppressor interacts with the protein AT rich interactive domain 4A (ARID4A, retinoblastoma-binding protein 1, RBBP1) as part of SIN3:histone deacetylase chromatin remodeling complexes. These transcriptional co-repressors regulate diverse cell phenotypes depending upon complex composition. To define BRMS1 complexes and their roles in metastasis suppression, we generated BRMS1 mutants (BRMS1^mut) and mapped ARID4A interactions. BRMS1^L174D disrupted direct interaction with ARID4A in yeast two-hybrid genetic screens (Y2H) but retained an indirect association with ARID4A in MDA-MB-231 and -435 human breast cancer cell lines by co-immunoprecipitation (co-IP). Deletion of the first coiled-coil domain (BRMS1^CC1) did not disrupt direct (Y2H) interaction, but did prevent association by co-IP. These results suggest altered complex composition with BRMS1mut. Although basal transcription repression was impaired and the pro-metastatic protein osteopontin (OPN) was differentially down-regulated by BRMS1^L174D and BRMS1^CC1, both down-regulated epidermal growth factor receptor (EGFR) and suppressed metastasis in MDA-MB-231 and -435 breast cancer xenograft models. We conclude that BRMS1mut that modify the composition of a SIN3:HDAC chromatin remodeling complex leads to altered gene expression profiles. Because metastasis requires the coordinate expression of multiple genes, down-regulation of at least one important gene, such as EGFR, had the ability to suppress metastasis. Understanding which interactions are necessary for particular biochemical/cellular functions may prove important for future strategies targeting metastasis.