Early detection of cancer is key to reducing morbidity and mortality. Morphological and chemical biomarkers presage the transition from normal to cancerous tissue.We have developed a noninvasive imaging system incorporating optical coherence tomography (OCT) and fluorescence lifetime imaging microscopy (FLIM) into a single optical system for the first time, in order to acquire both sets of biomarkers. OCT can provide morphological images of tissue with high resolution, while FLIM can provide biochemical tissue maps. Coregistered OCT volumes and FLIM images have been acquired simultaneously in an in vivo hamster cheek pouch model of oral cancer. The OCT images indicate morphological biomarkers for cancer including thickening of the epithelial layer and loss of the layered structure. The FLIM images indicate chemical biomarkers including increased nicotinamide adenine dinucleotide and reduced collagen emission. While both sets of biomarkers can differentiate normal and cancerous tissue, we believe their combination will enable the discrimination of benign lesions possessing some of the indicated biomarkers, e.g., scarring or inflammation. © 2010 IEEE.