Desmoplasia--the presence of a rich stroma around a tumor--has long been associated with a poor clinical outcome in patients with cancer. It is considered to be a response to the presence of invasive tumor cells. There is now evidence that desmoplasia is the result of coordinated changes in several stromal cells under the control of a single gene product, CD36, whose repression leads to a decrease in fat accumulation and an increase in matrix deposition. The presence of these changes in tumor-free human breast tissue strongly suggests that desmoplasia may precede and not always follow the presence of malignant cells. This concept has an important clinical implication for women at high risk of developing breast carcinoma, considering that the presence of desmoplasia in normal breast tissue detected in the form of mammographic density is one of the strongest risk factors.