Genetic analysis of breast tumor core needle biopsies may provide early diagnostic information that is useful to direct subsequent clinical management. We report metaphase comparative genomic hybridization (CGH) analysis of 42 core needle biopsies prospectively sampled from invasive ductal breast carcinomas of 41 patients, and show that recurrent chromosomal copy number changes are associated with histologically defined tumor features. As far as is known, this is the first time CGH profiles from diagnostic breast tumor core needle biopsies have been reported in association with pathological data in such detail. A comparison of Grade 1 (n = 7), Grade 2 (n = 16), and Grade 3 tumors (n = 19) revealed a chromosomal copy number gain involving 8q22 that was associated with higher grade (1/7 vs. 16/19, respectively) and therefore altered cell differentiation status. CGH results were validated using tumor touch imprints prepared from a subgroup from the same sample set (n = 18) by fluorescence in situ hybridization (FISH) and two probes selected from regions of interest within 8p21 and 8q22. Overall concordance between CGH and FISH for 8p21 and 8q22 imbalances was 9/18 (50%) and 12/18 (67%), respectively. When FISH and CGH data were combined, and tumors classified according to better defined resected tumor histology available for 34cases, 19/19 Grade 3 tumors showed 8q22 gain compared with 0/6 Grade 1 tumors and 4/9 Grade 2 tumors. Further comprehensive studies are required to verify the biological significance of this association and its potential to facilitate early clinicopathological assessment of breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2008 Wiley‐Liss, Inc.