An advanced hyper-spectral imaging (HSI) system has been developed for use in medical diagnostics. One such diagnostic, esophageal cancer is diagnosed currently through biopsy and subsequent pathology. The end goal of this research is to develop an optical-based technique to assist or replace biopsy. In this paper, we demonstrate an instrument that has the capability to optically diagnose cancer in laboratory mice. We have developed a real-time HSI system based on state-of-the-art liquid crystal tunable filter (LCTF) technology coupled to an endoscope. This unique HSI technology is being developed to obtain spatially resolved images of the slight differences in luminescent properties of normal versus tumorous tissues. In this report, an in-vivo mouse study is shown. A predictive measure of cancer for the mice studied is developed and shown. It is hoped that the results of this study will lead to advances in the optical diagnosis of esophageal cancer in humans.