Atherosclerosis is considered to be an inflammatory disease in which the initial process is the augmented infiltration of monocytes into the vessel wall and their subsequent differentiation from macrophages into lipid-laden foam cells. Human cartilage glycoprotein-39 (YKL-40) is a new inflammatory marker found to be secreted by lipid-laden macrophages inside human atherosclerotic vessel wall. The aim of this study was to investigate the association of serum YKL-40 levels with the presence and extent of coronary artery disease (CAD) assessed by coronary angiography. We also studied the relation of high-sensitivity C-reactive protein with the presence and angiographic severity of CAD. A total of 200 participants undergoing to coronary angiography was divided into four subgroups: control patients without CAD (n=53), and those with one-vessel disease (n=52), two-vessel disease (n=47), or three-vessel disease (n=48). Serum YKL-40 levels were measured by enzyme-linked immunosorbent assay. Both serum YKL-40 levels and high-sensitivity C-reactive protein concentrations in patients with CAD were significantly higher than in control participants (P < 0.001). We also found a significant association between the levels of YKL-40 and the extent of CAD defined by the number of stenosed vessels (P < 0.001). The relationship between the serum YKL-40 level and atherosclerosis may represent a new opportunity for the possible utility of serum YKL-40 as an inflammatory marker for coronary artery disease. Moreover, our findings revealed that plasma YKL-40 measurement might also be regarded as a quantitative indicator of disease extent besides being a marker of disease presence.