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Cyclins D1 and E play an important role in breast carcinogenesis. High cyclin E expression is common in hormone receptor negative and high grade aggressive breast cancer, whereas cyclin D1 in hormone receptor positive and low grade breast cancer. Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. To test this hypotheses in large breast cancer material and to clarify the histopathological correlations of cyclin E and D1, especially the association with proliferation, we analyzed cyclin E and D1 immunohistochemical expression on breast tumour microarrays consisting of 1348 invasive breast cancers. High cyclin D1 expression was associated with high grade (P, <, 0.0005), high cyclin A (P, <, 0.0005) and Ki67 (P, <, 0.0005) expression among ER positive but with low grade (P, =, 0.05) and low Ki67 (P, =, 0.01) expression among ER negative breast cancers. Cyclin E and D1 expression correlated positively in ER positive (P, <, 0.0005) but had a negative correlation in ER negative tumours (P, =, 0.004). Cyclin E associated with high grade among all tumours (P, <, 0.0005). In conclusion, the findings of this study show that cyclin D1 has separate roles, and proliferation is driven by different mechanisms in ER positive and negative breast cancers.