MYC and ERBB2 levels were measured in 38 benign breast diseases using a semiquantitative in situ hybridization technique. Mean levels of MYC and ERBB2 gene expression in benign tissues were similar to those measured in 15 breast cancers with no amplification at the loci concerned. Interestingly, MYC but not ERBB2 RNA levels were increased (t-test, P = 0.03) in benign mastopathies of patients with a first-degree (mother/sister) family history (FH) of breast cancer. Among patients without a first-degree FH, MYC RNA levels were significantly higher (t-test, P = 0.02) during the follicular (preovulatory) than the luteal (post-ovulatory) phase and also significantly higher than levels observed in patients with no menstrual cycle (peri- or postmenopausal) (P = 0.004), indicating an in vivo hormonal regulation of MYC. After exclusion of the first-degree FH patients a higher MYC expression was detected in atypia than in other histological types at the follicular but not at the luteal phase, suggesting an increased sensitivity of these high-risk lesions to estrogens. We propose that in addition to a family history and proliferative atypia, elevated MYC RNA levels during the post-ovulatory phase could potentially be used as a marker of the risk of developing breast cancer. The increase in MYC RNA in high-risk breast diseases also suggests that MYC deregulation might be involved in the early stages of mammary carcinogenesis.