Visualizing endogenous melanoma and bundled collagen throughout tumor development. Intravital multiphoton imaging of (i) melanoma expressing a tdTomato fluorescent reporter, and (ii) second harmonic generation enables direct observation of cancer cells and the extracellular matrix over time from early to late phases of tumor growth. Through intravital microscopy, it was found that collagen degrades as melanoma grows. However, when treated with MAPK inhibitors, bundled collagen reemerges to promote cancer resistance to drug. For details, see article by Brighton and colleagues on page 542.