We have measured genomic instability in invasive breast carcinomas and assessed the relationship of genomic instability to known tumor prognostic factors. DNAs from tumors and adjacent normal tissue of 18 breast cancer patients were subjected to inter-Simple Sequence Repeat (inter-SSR) PCR for quantitation of tumor genomic instability. Associations between genomic instability level and known breast cancer prognostic factors were evaluated using the Pearson Product Moment Correlation, the Kruskal–Wallis test of independent samples and the Mann–Whitney non-parametric test. Genomic instability was detected by inter-SSR PCR in over 90% of the breast tumors. The mean instability index was 3.08% (0–7.59%), approximately the same mean value observed in studies of colorectal and thyroid carcinomas. Significantly higher levels of instability were associated with tumors exhibiting necrosis. Genomic instability as measured is detected in the majority of breast cancers at levels comparable to other tumor types. Hypoxia, such as that observed in necrotic regions of tumors, has been associated with elevated genomic damage. We hypothesize that the higher levels of genomic instability detected in necrotic tumors is a consequence of hypoxia-associated DNA damage.