This study identifies microRNAs that suppress breast cancer metastasis. The authors found that restoring the expression of specific microRNAs in malignant cells suppressed lung and bone metastasis in vivo. Among these microRNAs, miR-126 and miR-335 were identified as key suppressors. MiR-126 reduced overall tumor growth and proliferation, while miR-335 inhibited metastatic cell invasion. MiR-335 regulates a set of genes associated with distal metastasis risk, including SOX4 and tenascin C. The loss of miR-335 and miR-126 expression is associated with poor distal metastasis-free survival in primary breast tumors. These findings highlight the role of miRNAs in suppressing breast cancer metastasis and suggest their potential as prognostic markers.This study identifies microRNAs that suppress breast cancer metastasis. The authors found that restoring the expression of specific microRNAs in malignant cells suppressed lung and bone metastasis in vivo. Among these microRNAs, miR-126 and miR-335 were identified as key suppressors. MiR-126 reduced overall tumor growth and proliferation, while miR-335 inhibited metastatic cell invasion. MiR-335 regulates a set of genes associated with distal metastasis risk, including SOX4 and tenascin C. The loss of miR-335 and miR-126 expression is associated with poor distal metastasis-free survival in primary breast tumors. These findings highlight the role of miRNAs in suppressing breast cancer metastasis and suggest their potential as prognostic markers.