Tibolone is a tissue-selective compound used for the treatment of climacteric symptoms and the prevention of osteoporosis in post-menopausal women. In this review some in vitro data and clinical studies indicating that the effects of tibolone on breast tissue are different from those seen with oestrogen-based hormone therapy (HT) are briefly discussed. From a clinical perspective, an increase in mammographic density and breast cell proliferation should be regarded as an unwanted side-effect of HT. Efforts should therefore be made to define treatment regimens for post-menopausal women that have minimal effects on the breast but still maintain the many advantages of HT. Data suggest that tibolone may be such an alternative.