Using a polymerase chain reaction based differential screening approach, we have isolated and characterised a cDNA from a human metastatic breast tumour representing a novel protein tyrosine kinase (brk). Sequencing of brk cDNAs isolated from T-47D and MCF-7 human breast tumour cell lines indicate that they encode a protein with the features of a novel nonreceptor tyrosine kinase, including amino terminal SH3 and SH2 domains. When synthesised in recombinant baculovirus and bacterial expression systems, brk protein products are capable of autophosphorylation on tyrosine residues. Initial expression studies have detected low levels of brk transcripts in some human breast tumours and breast tumour cell lines, but not in normal breast tissue.