To elucidate the role of CCND1 alterations in sporadic breast cancer we investigated the possible link between CCND1 mRNA levels versus estrogen-receptor (ER) status and a proliferation marker, S-phase fraction (SPF), measured by flow cytometry. CCND1 expression was quantified by means of real-time quantitative RT-PCR in a well-characterized series of 33 primary breast cancer patients. Eighteen tumors (54.5%) showed CCND1 overexpression ranging from 3.3 to 29.5 times the level observed in normal breast tissue. Seventeen (94.4%) of the 18 cases with CCND1 overexpression were ER-positive compared to seven (46.7%) of the 15 cases with normal CCND1 expression (p=0.0074). CCND1 overexpression was independent of SPF and DNA-ploidy status. These data suggest that the CCND1 gene does not act as an oncogene responsible for more rapid cell proliferation in breast cancer, but could be involved in the regulation of hormone sensitivity associated with ER.