Implicated in several physiologic processes, including tumour-host, some transglutaminases (TGase) have been noted to play a regulatory role in the extracellular matrix in cell adhesion and migration of cancer cells. This study sought to determine the level of expression of TGases and their possible clinical significance in a cohort of human breast cancer patients using RT-PCR and quantitative RT-PCR. Normal breast tissues generally expressed low levels of TGases-1, 2, 3 and 7, and higher levels of TGases-4, 5 and plasma TGase (FXIII). Significantly increased levels of transcripts of TGases-4 and 7, and significantly lower levels of FXIII were seen in tumour tissues (n= 110) compared with normal mammary tissues (n= 27), p= 0.05, 0.04 and 0.05, respectively. Node positive tumours exhibited significantly higher levels of TGase-2 and lower levels of TGase-3 (p= 0.05 and 0.046, respectively). The lowest levels of TGases-3 and 7 were seen in patients with metastatic disease, and TGase-3 in patients who died of breast cancer, compared with those who remained disease-free (median follow-up 72 months). Higher levels of TGases-4 and 5 were noted in patients with local recurrence. Breast cancer displays an aberrant expression of TGases, wherein the levels of TGases-2, 3 and 7 have a relationship with node involvement and patient outcome.