Background: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, and the underlying molecular mechanisms are not clear. To date, few studies have been conducted on the altered expression of serum microRNAs (miRNAs) in women with PCOS. The present study was performed to examine the role of the serum miRNA as a biomarker for the diagnosis of PCOS and its relationship with metabolic and reproductive traits. Methods: A cross-sectional comparison was made in 21 women with PCOS and age- and body mass index (BMI)- matched 21 healthy women in an academic center laboratory between December 2008 and October 2010. We selected miRNAs that were more than 1.5-fold upregulated or less than 0.67-fold down-regulated in women with PCOS compared with controls using the SurePrint G3 Human miRNA Microarray. Subsequently, we validated the relative expression of the miRNAs using TaqMan quantitative real-time polymerase chain reaction (RT-qPCR) assays. Results: Serum miRNA-4522, miRNA-324-3p, and miRNA-6767-5p were down-regulated in women with PCOS compared with controls in the microarray analysis. Among these miRNAs, serum miRNA-6767-5p was validated (fold change in women with PCOS/controls = 0.39, P-value<0.05) by RT-qPCR. The miRNA-6767-5p was negatively associated with fasting glucose (β = -0.370) and positively associated with the number of menses per year (β = 0.383) after adjustment for age and BMI (Ps<0.05). Genes targeted by miRNA-6767-5p were involved in the cell cycle and the immune system. Conclusions: Serum miRNA-6767-5p may be a novel candidate as a molecular biomarker in the diagnosis of PCOS and may participate in the development of the metabolic and reproductive traits of PCOS.