Fourier-Transform Infrared Spectroscopy (FTIR) employs a unique approach tooptical diagnosis of tissue pathology based on the characteristic molecularvibrational spectra of the tissue. The biomolecular changes in the cellularand sub-cellular levels developing in abnormal tissue, including a majorityof cancer forms, manifest themselves in different optical signatures, whichcan be detected in infrared microspectroscopy. This report has two parts. Inthe first part, we report studies on normal, premalignant (polyp) andmalignant human colonic tissues from three patients with different stages ofmalignancy. Our method is based on microscopic infrared study (FTIR-microscopy)of thin tissue specimens and a direct comparison with traditional histopathologicalanalysis, which serves as a “gold” reference. The limited dataavailable showed normal colonic tissue has a stronger absorption thanpolypoid tumor and cancerous types over a wide region in a total of 100measurements. Detailed analysis showed that there is a significant decreasein total carbohydrate, phosphate and possibly creatine contents for polyp andcancerous tissue types in comparison to the controls. The same trend is maintainedin seven other patients studied. The second part consists of an analysis showingthe influence of various independent factors such as age, sex and grade of malignancy. Ourpreliminary results suggest that among the above three factors, age and gradeof malignancy have significant effect on the metabolites level, but sex has onlyminor effect on the measured spectra. Initial results on Linear DiscriminantAnalysis (LDA) showed good classification between normal and malignant cellsof human colonic tissues.