Copy number variation (CNV) is crucial for gene regulation in humans. A number of studies have revealed that CNV contributes to the initiation and progression of cancer. In this study, we analysed four breast cancer cell lines and six fresh frozen tissues from patients to evaluate the CNV present in the genome using microarray-based comparative genomic hybridization (aCGH). Six genes located at 16q22.1 were analysed by real-time PCR. The real-time PCR analysis revealed that the loss of CDH1/E2F4 may be associated with worse clinical and pathological findings. Interestingly, covariation of CDH1, CDH3, CTCF and E2F4 was found to be associated with triple negative breast cancer and HER-2 receptor status. In conclusion, our study supports the idea that CNV at 16q22.1 in breast cancer is a frequent event; furthermore, it reveals the covariation of CDH1, CDH3, CTCF and E2F4. The role of the covariation is more complex than a simple additive effect of these four separate genes, which may provide a novel target for breast cancer.