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The combination of low-coherence interferometry with angle-resolved light scattering measurements has been shown to be a powerful method for determining the structure of cell nuclei within intact tissue samples. The nuclear morphology data have been used as a biomarker of neoplastic change in a wide range of settings. Here, we review the development of angle-resolved low-coherence interferometry (a/LCI) for assessing the health status of human esophageal epithelial tissues based on depth-resolved measurements of the morphology of cell nuclei. The design and implementation of clinical instrumentation are reviewed, and results from ex vivo human tissue measurements are presented to validate the capabilities of the technique. In addition to the review of earlier papers, new results are presented, which demonstrate the first application of a portable a/LCI system with a flexible endoscopic probe to assessing depth-resolved nuclear morphology in a clinical setting. High sensitivity for the detection of precancerous tissues is demonstrated. [ABSTRACT FROM PUBLISHER]