Background: Pyruvate kinase isoenzyme M2-PK is instrumental to tumour metabolism and hence over-expressed in tumour cells leading to detectable plasma concentrations. Objective: To assess the degree of association between M2-PK plasma concentrations and ovarian cancer and to determine the cut-off values for its sensitivity and specificity for differentiating between benign and malignant ovarian disease. Settings: The Gynaecological Cancer Centre at both King's College and St Thomas' Hospital, London, UK. Methods: Patients with suspected ovarian cancer referred to the above centre were recruited prospectively during the years 2004- 2005. Blood samples were collected before surgery for analysis plasma M2-PK assays. Results were assessed with respect to cancer was diagnosis, patient and tumor characteristics. Statistical analysis including the receiver operator characteristic(ROC) curve was performed using Analyse It^® and SPSS V13^®. Results: 100 patients with age range 14-88 years and a median of 57 years were recruited in the study. Of whom were diagnosed with invasive ovarian cancer. Of these 35(67%) were Stage III and above with two secondary. M2-PK was not related patient age (p = 0.43). There was a significant correlation between CA125 and M2-PK (p < 0.001). The mean M2-PK concentration in cancer patients was 52 U/ml versus 27U/mL in patients with benign conditions (p < 0.001). At a cut-off value of 22U/ml the sensitivity of M2-PK for detecting cancer was 70% with a specificity of 65%. Conclusion: M2-PK was significant raised in ovarian cancer patients, however its role in clinical practice needs further evalution.