Over-expression of a centrosomal serine/threonine kinase, STK15/BTAK, induces centrosome amplification, which results in chromosomal instability (CIN) in cell culture. In the present study, we investigated the correlation of STK15/BTAK mRNA expression with CIN and various clinicopathological factors in human breast cancer. STK15/BTAK mRNA levels were quantified by real-time PCR, and CIN values were determined by FISH analysis of chromosomes 1, 11 and 17 using centromeric probes. STK15/BTAK mRNA levels (0.310 +/- 0.413, mean +/- SD, n = 47) in breast cancers were significantly (p < 0.01) higher than those in normal breast tissues (0.044 +/- 0.029, n = 9). Furthermore, breast cancers were divided into 3 groups (low, intermediate and high) according to STK15/BTAK mRNA expression levels. CIN values of the low-expression group (27.9 +/- 12.6%, n = 18) were significantly (p < 0.01) higher than those of normal breast tissues (9.2 +/- 2.6%, n = 6), and those of the high-expression group (38.0 +/- 12.7%, n = 14) were significantly (p < 0.05) higher than those of the low-expression group. STK15/BTAK mRNA expression showed a significant (p < 0.05) correlation with high histological grade and negativity of estrogen and progesterone receptors. Our results demonstrate that STK15/BTAK mRNA is over-expressed in the majority of breast cancers and its over-expression is significantly associated with CIN, implicating STK15/BTAK in carcinogenesis through induction of CIN. STK15/BTAK mRNA levels might be useful as an indicator of poor prognosis and resistance to endocrine therapy.