Cell-free DNA has been shown to have diagnostic potential in a number of malignant diseases. Recently, the integrity or size distribution of these fragments has also been identified as having possible diagnostic value. The current study explores the role of this novel parameter in the clinical diagnosis of prostate cancer. Plasma samples, collected prospectively from men undergoing investigation for prostate cancer, were used to obtain a cell-free DNA sample. Real-time PCR was used to quantify the level of cell-free DNA (ng/ml) and its size distribution (delta CD in each case. Sixty-one samples were collected from patients with prostate cancer and 62 from those with benign histology. Analysis failed to reveal a statistically significant relationship between either the level of cell-free DNA (p = 0.82) or its size distribution (p = 0.91) and the presence of cancer. These results demonstrate that cell-free DNA is unlikely to be of diagnostic value in the clinical management of this disease.