The relationship between use of non-contraceptive oestrogens and risk of breast cancer was investigated using data from a hospital-based case-control study from Northern Italy. This study covered 1,108 patients with histologically confirmed breast cancers and 1,281 control subjects with a large spectrum of acute conditions unrelated to any of the known or suspected risk factors for breast cancer. Compared with “never-users”, the age-adjusted relative risk for “ever-users” was 1.93 (95% confidence interval = 1.35–2.75). The risk increased with duration of use (relative risk = 2.08 for over 2 years), but was unrelated to time elapsed since first or last use. Allowance for a large number of identified potential confounding factors, including indicators of socio-economic status and the major determinants of breast cancer risk, failed to account for the observed association (multivariate relative risk = 1.84 for ever use and 2.04 for > 2 year use). Possible explanations for these findings and for their apparent discrepancy with some American data are discussed in terms of different baseline incidence of breast cancer in the two populations, and hence of potential baseline differences in availability of endogenous serum oestrogens. Nonetheless, the results of this study should be interpreted cautiously and viewed as a further contribution to a topic still open to debate.