The Coxsackie-adenovirus receptor (CAR) is the primary site for adenovirus attachment during infection and has been used as a delivery mechanism for gene therapies. However, the expression profile of the receptor in cancer, particularly in clinical breast cancer, is poorly reported. This study evaluated the expression of CAR in human breast cancers. Frozen sections from breast cancer primary tumours (matched tumour n=114 and background n=30) were immunostained with CAR antibody. RNA was reverse transcribed and analysed by quantitative-PCR (Q-PCR). Levels of CAR were analysed against the clinical background, with a median follow-up of 72 months. Staining intensity of CAR was increased within tumour sections compared to background tissue. Q-PCR revealed significantly elevated levels of CAR transcript in breast tumours (32 313+/-7067 mean+/-SE vs. background tissue 11 483+/-7069, P=0.023). CAR expression also increased with grade of tumour. Patients who had tumour metastases also showed elevated levels of CAR expression (metastasis: 61 940+/-22 749 vs. alive and well 29 655+/-8149), however those with local recurrences had reduced levels of CAR. Ductal carcinomas expressed lower levels of CAR compared to tumours of other types. Tumours with nodal involvement were also associated with higher levels of CAR (node positive 2320 median vs. node negative 1077.5). Levels of CAR were significantly correlated with long-term survival over a period of 6 years (P=0.004, univariate analysis). We conclude that CAR expression is elevated in primary breast cancers. This may have a bearing on its use as means of delivery for gene therapy and suggests that further work is necessary to understand this complex molecule.