Background: Breast cancer is the most common form of malignancy affecting women worldwide. It is also the leading cancer in females in Cyprus, with approximately 400 new cases diagnosed annually. It is well recognized that genetic variation as well as environmental factors modulate breast cancer risk. The main aim of this study was to assess the strength of associations between recognized risk factors and breast cancer among Cypriot women. This is the first epidemiological investigation on risk factors of breast cancer among the Cypriot female population.Methods: We carried out a case-control study, involving 1,109 breast cancer patients and a group of 1,177 controls who were recruited while participating in the National screening programme for breast cancer. Information on demographic characteristics and potential risk factors were collected from both groups during a standardized interview. Logistic regression analysis was used to assess the strength of the association between each risk factor and breast cancer risk, before and after adjusting for the possible confounding effect of other factors.Results: In multivariable models, family history of breast cancer (OR 1.64, 95% CI 1.23, 2.19) was the strongest predictor of breast cancer risk in the Cypriot population. Late menarche (OR 0.64, 95% CI 0.45, 0.92 among women reaching menarche after the age of 15 vs. before the age of 12) and breastfeeding (OR 0.74, 95% CI 0.59, 0.92) exhibited a strong protective effect. In the case of breastfeeding, the observed effect appeared stronger than the effect of pregnancy alone. Surprisingly, we also observed an inverse association between hormone replacement therapy (HRT) although this may be a product of the retrospective nature of this study.Conclusion: Overall the findings of our study corroborate with the results of previous investigations on descriptive epidemiology of risk factors for breast cancer. This investigation provides important background information for designing detailed studies that aim to improve our understanding of the epidemiology of breast cancer in the Cypriot population, including the study of gene-environment interactions. Furthermore, our study provides the first scientific evidence for formulating targeted campaigns for prevention and early diagnosis of breast cancer in Cyprus.