Recently, cyclin-E was reported to be the most prominent prognostic factor for breast cancer outcome described so far, even surpassing axillary nodal involvement. Earlier studies on the prognostic value of cyclin-E in breast cancer, however, yielded heterogeneous results. Therefore, we set out to confirm and extend these results by quantitative Taqman RT-PCR of cyclin-E levels in 277 resectable breast cancers. Cyclin-E levels were not associated with relapse-free survival (RFS) or overall survival (OS) in the total cohort of patients, or in the subset of patients without involved lymph nodes that were not treated with adjuvant systemic therapy. Besides several classical clinicopathological factors, the interaction between cyclin-E and adjuvant endocrine therapy (P=0.01, HR=3.04, 95% CI: 1.30-7.09) was found to contribute significantly in multivariate analyses. Cyclin-E levels were associated with poor RFS specifically in patients treated with adjuvant endocrine therapy (n=108, P=0.001, HR=4.01, 95% CI: 1.76-9.12), independent of estrogen receptor status. In conclusion, cyclin-E is not a pure prognostic factor in breast cancer, but rather a predictor of failure of endocrine therapy. Differences in literature on the presumed prognostic value of cyclin-E may be due to differences in treatment. Assessment of cyclin-E levels can aid in improving adjuvant treatment selection.