This study investigates the role of collagen reorganization at the tumor-stromal interface in facilitating local invasion in breast tissue. Using multiphoton laser-scanning microscopy (MPLSM) and second harmonic generation (SHG) imaging, the authors examined the organization of collagen structures around ducts and tumors in intact, unfixed, and unsectioned mammary glands. They identified three tumor-associated collagen signatures (TACS) that provide markers for locating and characterizing tumors. TACS-1 is characterized by dense collagen near the tumor, TACS-2 by "taut" collagen fibers stretched around the tumor, and TACS-3 by collagen fibers aligned normal to the tumor boundary, indicative of local invasion. The authors found that tumor cells can realign a random collagen matrix to facilitate invasion, suggesting that matrix reorganization at the tumor interface plays a crucial role in tumor progression. This study highlights the importance of collagen organization in breast cancer development and provides a potential diagnostic tool for identifying and characterizing breast tumors.This study investigates the role of collagen reorganization at the tumor-stromal interface in facilitating local invasion in breast tissue. Using multiphoton laser-scanning microscopy (MPLSM) and second harmonic generation (SHG) imaging, the authors examined the organization of collagen structures around ducts and tumors in intact, unfixed, and unsectioned mammary glands. They identified three tumor-associated collagen signatures (TACS) that provide markers for locating and characterizing tumors. TACS-1 is characterized by dense collagen near the tumor, TACS-2 by "taut" collagen fibers stretched around the tumor, and TACS-3 by collagen fibers aligned normal to the tumor boundary, indicative of local invasion. The authors found that tumor cells can realign a random collagen matrix to facilitate invasion, suggesting that matrix reorganization at the tumor interface plays a crucial role in tumor progression. This study highlights the importance of collagen organization in breast cancer development and provides a potential diagnostic tool for identifying and characterizing breast tumors.