Breast cancer (BC) is one of the most common cancers in females. Since early detection can bring prognosis benefit, discovery of novel noninvasive biomarkers for BC diagnosis is in urgent need. In this four-phase study, we profiled miRNA expression in plasma samples from a total of 257 BC patients and 257 normal controls (NCs). Exiqon miRNA qPCR panel was used to select candidate miRNAs in the screening phase which were further analyzed using qRT-PCR in the following training, testing and external validation phases. Finally, we identified five plasma miRNAs (let-7b-5p, miR-122-5p, miR-146b-5p, miR-210-3p and miR-215-5p) whose expression levels were significantly different between BC patients and NCs. A 5-miRNA panel in plasma with high sensitivity and specificity was then constructed to detect BC. The areas under the receiver-operating characteristic curves (AUCs) of the panel were 0.683, 0.966, 0.978 for the training, testing and external validation sets, respectively. Expression of the identified miRNAs was further analyzed among 32 pairs of BC tissue and the adjacent normal tissue samples as well as plasma-derived exosome samples from 32 BC patients vs 32 NCs. Let-7b-5p was contrarily down-regulated in BC tissue. In exosomes samples, only miR-122-5p was significantly up-regulated as in plasma for BC patients. In conclusion, we identified a 5-miRNA plasma panel (let-7b-5p, miR-122-5p, miR-146b-5p, miR-210-3p and miR-215-5p) that could serve as a promising biomarker for BC detection.