We describe a system capable of measuring spatially resolved reflectance spectra from 380 to 950 nm and fluorescence excitation emission matrices from 330 to 500 nm excitation and 380 to 700 nm emission in vivo. System performance was compared to that of a standard scanning spectrofluorimeter. This 'FastEEM' system was used to interrogate human normal and neoplastic oral cavity mucosa in vivo. Measurements were made through a fiber-optic probe and require 4 min total measurement time. We present a method based on autocorrelation vectors to identify excitation and emission wavelengths where the spectra of normal and pathologic tissues differ most. The FastEEM system provides a tool with which to study the relative diagnostic ability of changes in absorption, scattering, and fluorescence properties of tissue.