A method for using acetic acid as a contrast agent during reflectance confocal imaging of normal and neoplastic tissue, particularly epithelium. In one aspect, the invention includes a method of using acetic acid as a contrast agent for confocal imaging of cells, including applying acetic acid to the diagnostic tissue sample in sufficient concentration to induce a small scale alteration of the index of refraction of nuclei in the cells; and imaging such cells using a reflectance confocal imaging system.