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Background Lipocalin-2 is a novel adipokine that appears to play a role in the development of insulin resistance. Serum lipocalin-2 levels are elevated in obese patients. Obesity and insulin resistance are cardinal characteristics of the polycystic ovary syndrome (PCOS). However, there are limited data on serum lipocalin-2 levels in patients with PCOS. The aim of the present study was to assess serum lipocalin-2 levels in PCOS. Methods We studied 200 patients with PCOS and 50 healthy female volunteers. Results Serum lipocalin-2 levels were slightly higher in women with PCOS compared with controls (65.4 +/- 34.3 vs. 60.3 +/- 26.0 ng/ml, respectively) but this difference did not reach statistical significance. In contrast, lipocalin-2 levels were higher in overweight/obese women with PCOS than in normal weight women with the syndrome (76.2 +/- 37.3 vs. 54.5 +/- 27.2 ng/ml, respectively; p < 0.001). Serum lipocalin-2 levels were also higher in overweight/obese controls compared with normal weight controls (70.1 +/- 24.9 vs. 50.5 +/- 23.7 ng/ml, respectively; p = 0.004). In the total study population (patients with PCOS and controls), lipocalin-2 levels were independently correlated with the body mass index (p < 0.001). In women with PCOS, lipocalin-2 levels were independently correlated with the waist (p < 0.001). Conclusions Obesity is associated with elevated serum lipocalin-2 levels. In contrast, PCOS does not appear to affect lipocalin-2 levels.