Aim: Sarcosine has been identified as a differential metabolite that is greatly increased during progression from normal tissue to prostate cancer and metastatic disease. In this study we assessed the role of serum sarcosine in metastatic castration-resistant prostate cancer (mCRPC) patients. Patients & methods: Data from 52 mCRPC patients treated with docetaxel-based chemotherapy were retrospectively analyzed. Receiver operating characteristic curves, and Kaplan–Meier and Cox multivariate analyses were performed. Results: Median sarcosine values were significantly higher in mCRPC versus non-mCRPC patients (0.81 vs 0.52 nmol/µl; p < 0.0001). A significant correlation resulted between serum sarcosine levels and the duration of hormone sensitivity (Spearman’s correlation coefficient: -0.51; p = 0.001). At multivariate analysis sarcosine was an independent prognostic factor of outcome in terms of overall and progression-free survival. Conclusion: Serum sarcosine values were significantly increased in patients with metastatic disease. Moreover, this biomarker is a risk factor for progression and survival in chemotherapy-treated mCRPC patients.