Highly unsaturated fatty acids (HUFAs) are cyto-toxic to cancer cells and generated in the body by desaturation from essential fatty acids, primarily involving delta-6-desaturase. This study, for the first time, examined the level of expression of human delta-6-desaturase as well as delta-4-desaturase in human breast cancer. Breast tumours (n=102) which comprised of 88 ductal and 14 lobular carcinomas, as well as normal breast tissues (n=31), together with breast cancer cell lines were analysed for the level of expression of delta-6- and delta-4-desaturases using RT-PCR and quantitative PCR. A lower level of delta-6-desaturase was seen in breast tumour compared with normal tissues. Tumours from patients who had a poor prognostic index and from those who died of breast cancer had the lowest level of delta-6-desaturase (median follow-up 72 months). In addition, TNM3 and TNM4 tumours had significantly lower level of delta-6-desaturase than TNM1 tumours. Interestingly, ductal tumours displayed significantly higher level of the enzyme than lobular tumours. In contrast, a stepwise increase of delta-4-desaturase was seen in tumour from patients with poor prognosis. It is concluded that aggressive breast tumours have a reduced level of delta-6-desaturase. This aberrant expression has clinical bearings to the outcome in patients with breast cancer.