A 44-year-old man with symptoms of ocular irritation and corneal changes characteristic of Salzmann's nodular degeneration in the left eye was examined using in vivo confocal microscopy. In vivo confocal microscopy highlighted an irregularly shaped basal epithelium with foci of prominent nuclei, and disrupted anterior stromal architecture with increased reflectivity of extracellular matrix within the nodules. These observations were consistent with prior histopathological descriptions of Salzmann's nodular degeneration. In vivo confocal microscopy enhances the clinicopathological assessment of degenerative corneal diseases, such as Salzmann's nodular degeneration, without the need for biopsy.