Optical coherence tomography (OCT)/optical Doppler tomography (ODT) provides real-time in vivo high-resolution (10-μm) imaging of tissues and real-time spatially resolved blood flow in microvasculature. Hamster cheek pouches with induced dysplasia and malignancies were imaged with OCT/ODT to assess the potential for application to airway malignancy. In 22 Golden Syrian hamsters, 0.5% 9,10-dimethyl-1,2-benzanthracene induces carcinogenesis over 10 weeks in right side cheek pouches; the left side three served as controls. The cheek pouches are imaged in vivo prior to sacrifice, and in vitro after excision, using a prototype 1310-nm broadband superluminescent diode based OCT/ODT device. Images are compared to standard histopathology. OCT imaging offers good resolution of the hamster cheek pouches to depths of 1 to 3 mm and paralleled histologic images. The feasibility of high-resolution functional imaging is demonstrated in this hamster cheek pouch tumor model. ODT accurately detects vascular change associated with carcinogenesis. © 2004 Society of Photo-Optical Instrumentation Engineers.