We analyzed loss of heterozygosity (LOH) and microsatellite instability (MI) in 108 cases of sporadic breast cancers using 22 microsatellite markers on 12 chromosomes. LOH was frequently seen in 1p(13%), 6p(18%), 8p(11%), 11p(18%), 13q(21%),16q(31%), 17p(44%) and 17q(29%). Individual patients were scored according to the degree of LOH at the above eight chromosomal markers. Patients with no LOH were scored as 1, patients with one to three LOH were scored as 2, and patients with four or more LOH were scored as 3. A high LOH score correlated with a high histological grade (p=0.019) and a poor prognosis (p=0.0035). Eleven(10.2%) of 108 patients with breast cancer showed MI, with 6 cases showing MI at a single locus and 5 at multiple loci. Of the 11 MI-positive patients only one had lymph node involvement(p=0.015), none had histological grade 3 disease, and MI-positive patients tended to have a better prognosis than MI-negative ones. These data suggest that MI may be an early event in mammary tumorigenesis, and that LOH occurs at a later stage. The LOH score may be a useful prognostic marker of operable breast cancer.