Uterine leiomyoma is the most common benign smooth muscle tumor in women pelvis, originating from the myometrium. It is caused by a disorder of fibrosis, with a large production and disruption of extracellular matrix (ECM). Medical treatments are still very limited and no preventative therapies have been developed. We supposed that synchrotron-based phase-contrast microtomography (PhC-microCT) may be an appropriate tool to assess the 3D morphology of uterine leiomyoma, without the use of any contrast agent. We used this technique to perform the imaging and the quantitative morphometric analysis of healthy myometrium and pathologic leiomyomas. The quantitative morphometric analysis of collagen bundles was coupled to the Roschger approach. This method, previously only used to evaluate mineralized bone density distribution, was applied here to study the fibrosis mass density distribution in healthy and pathologic biopsies from two patients. This protocol was shown to be powerful in studying uterine leiomyomas, detecting also small signs of the ECM alteration. This is of paramount importance not only for the follow-up of the present study, i.e. the investigation of different compounds and their possible therapeutic benefits, but also because it offers new methodologic possibilities for future studies of the ECM in soft tissues of different body districts. Uterine leiomyoma (myoma or fibroid) is the most common benign smooth muscle tumor in women pelvis causing significant morbidity in a large segment of reproductive-aged women 1,2 , including significant impact on the reproductive healthy status and on the pregnancy outcome of affected patients 3,4. Fibroids remain the leading indication for hysterectomy 5,6 especially during the peri-menopause period, although the assumption that leiomyoma symptoms will resolve with the onset of the menopause is too simplistic and may not be always valid 7. Medical treatments for leiomyoma are still very limited and no preventative therapies have been developed 8. The precise pathogenesis of uterine leiomyoma is not well understood. Genetic alterations, epigenetic mechanisms, steroids, growth factors, cytokines and chemokines provide the clue of initiators and promoters of leiomyoma growth 9. Uterine myoma is thought to be a consequence of myofibroblasts activation and extracellular matrix (ECM) production, following an improper inflammatory response inside the myometrium 10-12. Excessive accumulation of ECM components including collagens, fibronectin and proteoglycans are the major structural part of leiomyoma tissue that are abnormally orientated modifying mechanical stress on cells and leading to activation of internal mechanical signaling and dynamic reciprocity 13-15. The ECM stiffness causes the rigid structure of the leiomyoma and it is thought to be a cause of abnormal bleeding and pelvic pressure and pain 16. The role of inflammation and reparative processes as well as the effect of some potential therapeutic compounds (tranilast, strawberry extracts, omega-3 fatty acids, g...