Purpose: Optical coherence tomography (OCT) is a minimally invasive, depth-resolved imaging tool that can be commissioned for small diameter endoscopic applications for imaging mouse models of colorectal cancer. In this study, we utilized ultrahigh resolution OCT (UHR OCT) to serially image the lower colon of azoxymethane (AOM) treated A/J mouse models of CRC, monitor the progression of neoplastic transformations, and determine if OCT is capable of identifying early disease. Experimental Design: Thirteen AOM treated A/J and two control A/J mice were surveyed at four timepoints (8, 14, 22, and 26 weeks post AOM treatment) using a prototype 2.0 mm diameter UHR OCT endoscope-based system that achieved resolutions of 3.2 urn axial and 4.4 urn lateral. Histological samples were obtained at the final imaging timepoint serving as the gold standard. Results: Gross and histological assessment of the excised colonie tissue revealed at least one tumor in all 13 AOM treated mice, with most mice developing multiple tumors. In the corresponding OCT images, a progression from healthy thin mucosa to adenoma appearing as large, structurally disorganized masses was visualized over the imaging time points correlating to the locations of the grossly visualized tumors. Conclusions: This study indicates that UHR OCT enables accurate identification of disease and non-destructive visualization of CRC progression in the lower colon of mice.