Loss of heterozygosity (LOH) at the deleted in colorectal carcinoma gene (DCC), a tumour suppressor gene that encodes a protein with high homology to the neural cell adhesion molecule, was investigated in 42 surgical specimens of primary breast carcinoma. LOH was analysed in breast carcinoma by amplifying the DNA, spanning a variable number of tandem repeats site and a restriction fragment length polymorphism site within DCC, using the polymerase chain reaction (PCR). Cell sorting was used to enrich carcinoma cells. The expression of the DCC gene was also investigated using a reverse transcription-PCR method followed by Southern blot hybridization. LOH at the DCC locus was detected in 15 (51.7%) of 29 informative cases and 10 of 13 cases having DCC-LOH showed distinct reduction or loss of DCC expression. The DCC-LOH was closely associated with certain histological phenotypes: DCC-LOH was more frequent in scirrhous carcinomas than in solid-tubular ones (P < 0.05), and was also more frequent in carcinomas with infiltration into fat tissue over the mammary gland than in those without infiltration (P < 0.05). DCC-LOH was detected in invasive lobular carcinomas (2/2), but in none of the noninvasive ductal carcinomas (0/2). These observations suggest that malignant histological phenotypes are associated with DCC-LOH.