Background: Polycystic ovarian syndrome (PCOS) is a chronic endocrinopathy of unexplained etiology linked to obesity. Neuregulin 4 (NG-4) is an adipokine synthesized primarily by brown adipose tissue; that keeps glucose and lipids in hemostasis. Earlier research tested serum NG-4 correlation with metabolic parameters in PCOS; herein, we aimed to examine serum NG-4 validity as a marker for PCOS with respect to obesity parameters and the influence of obesity on NG-4 concentrations. Methods: A cross-sectional study recruited 120 women into two groups; PCOS cases (60/120) and healthy controls (60/120). For every participant, three sets of data were recorded; anthropometric data (age, height, and weight for calculation of body mass index (BMI), waist/hip ratio, and systolic and diastolic blood pressure) hormonal levels, including serum (luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, prolactin, anti-Mullerian hormone (AMH), testosterone, and insulin) and biochemical biomarkers (fasting blood sugar, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), high and low-density lipoproteins (HDL and LDL), and NG-). Results: Serum NG-4 levels were significantly higher among PCOS vs. healthy controls. The univariant analysis confirmed a significant correlation of NG-4 to BMI, hormonal, and metabolic parameters. None of the obesity parameters were correlated with serum NG-4; only PCOS had an effect on serum NG-4 with p 0.001 in multivariate analysis. At a cutoff value of 32 (ng/mL), NG-4 showed the highest sensitivity and specificity in discriminating PCOS cases with an area under the curve (AUC) of 0.97, p 0.001. Conclusions: Serum NG-4’s strong relation to hormonal and biochemical parameters that define PCOS independent of BMI and waist-to-hip ratio makes it a reliable biomarker in diagnosing and following up PCOS cases.