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Purpose. The aim of this study was to develop a highly sensitive powder X-ray diffraction (XRD) technique for quantification of crystallinity in substantially amorphous pharmaceuticals, utilizing synchrotron radiation and a 2-D area detector. Methods. Diffraction data were acquired at the European Synchrotron Radiation Facility (France) using a 2-D charge-coupled device detector. The crystallization of amorphous sucrose was monitored in situ, isothermally at several temperatures in the range of 90 to 160-C. An algorithm was developed for separation of the crystalline and amorphous intensities from the total diffraction pattern. Results. The synchrotron XRD technique allowed powder diffraction patterns to be recorded with a time resolution of 40 ms. The gradual crystallization of sucrose is analogous to a series of physical mixtures with increasing content of the crystalline component. The in situ crystallization approach circumvented the problem of inhomogeneity in mixingVa potentially serious issue at extreme mixture compositions. The estimated limit of detection of crystalline sucrose in an amorphous matrix was 0.2% w/w, a considerable improvement over the reported value of õ1% w/w with a conventional XRD. Conclusion. High-intensity XRD can discern subtle changes in the lattice order of materials. The first evidence of crystallization can serve as an indicator of the potential physical instability of the product.