BACKGROUND YKL-40 is a growth factor for connective tissue cells; it also stimulates the migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum levels have been associated with poorer prognosis in metastatic breast cancer. In the present study we evaluated the prognostic role of serum YKL-40 levels in patients with locally advanced breast cancer. METHODS YKL-40 levels were measured using ELISA in serum samples obtained from 45 breast cancer patients prior to surgery and chemotherapy. The median follow-up time was 46 months (range, 10-96 months). All patients underwent surgery after chemotherapy. During the follow-up period, 21 patients relapsed and there were 17 deaths. RESULTS The median serum YKL-40 concentration in patients with locally advanced breast cancer was 149.5 mug/l (range, 25.0-1021.3 microg/l). This was higher than levels observed in healthy female controls but the difference was not significant (P=0.44). Serum YKL-40 levels were also higher in patients with tumour size >2 cm and node-positive disease but again the differences were not significant (P>0.05). Tumour volume was correlated with serum YKL-40 levels (r=0.308, P=0.039). High serum YKL-40 levels were associated with shorter disease-free and overall survival although this trend failed to reach significance (P>0.05). Multivariate analysis including tumour size, lymph node status, oestrogen and progesterone receptor status, tumour grade, and serum YKL-40 levels indicated that serum YKL-40 levels were an independent prognostic variable for overall survival (hazard ratio, 1.004; 95% confidence intervals: 1.00, 1.07; P=0.027). Tumour size, lymph node status and oestrogen receptor status were also independent prognostic variables for overall survival (P<0.05). CONCLUSIONS Our results show that serum levels of the growth factor YKL-40 may be a useful prognostic indicator of outcome for patients with locally advanced breast cancer. Further studies are required to fully elucidate the biological function of YKL-40 in breast cancer.