Finally, the optimal protein combinations for the diagnosis of breast cancer were PON3, IGLV3‐10, and IGHV3‐73 through multi‐model analysis, which had a high prediction accuracy for breast cancer (AUC = 0.92), and the model could also distinguish breast cancer from HC (AUC = 0.92) and breast cancer from benign breast tumor (AUC = 0.91). Here, PON3 is linked to breast benign neoplasm.